Fungicidal composition and method for controlling plant diseases

ABSTRACT

A fungicidal composition containing, as active ingredients, (a) a benzoylpyridine derivative represented by the following formula or its salt:  
                 
 
wherein X is a halogen atom, a nitro group, a substitutable hydrocarbon group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group, a hydroxyl group, a substitutable alkylthio group, a cyano group, a carboxyl group which may be esterified or amidated, or a substitutable amino group, n is 1, 2, 3 or 4; R 1  is a substitutable alkyl group, R 2′  is a substitutable alkyl group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group or a hydroxyl group, p is 1, 2 or 3, and R 2″  is a substitutable alkoxy group or a hydroxyl group, provided that at least two of R 2′  and R 2″  optionally form a condensed ring containing an oxygen atom and (b) at least one other fungicide.

TECHNICAL FIELD

The present invention relates to a fungicidal composition useful as anagricultural and horticultural fungicide having remarkably improvedpreventive and/or curative effects against plant diseases, and a methodfor controlling plant diseases by using such a composition.

BACKGROUND ART

WO02/2527 discloses that a benzoylpyridine derivative which is an activeingredient of the fungicidal composition in the present invention isuseful as a fungicide and may be used in combination with anotherfungicide as the case required. However, it has not been known that thecomposition of the present invention has a remarkably excellentfungicidal effect.

Patent Document 1: WO02/2527

DISCLOSURE OF THE INVENTION PROBLEMS THAT THE INVENTION IS TO SOLVE

Each of benzoylpyridine derivatives represented by the formula (I) givenhereinafter, may have an inadequate controlling effect against aspecific plant disease, its residual effect may last only a relativelyshort time or its rainfastness may be weak, and it has only aninadequate controlling effect against plant diseases practicallydepending upon the application site.

MEANS OF SOLVING THE PROBLEMS

The present inventors have conducted a research to solve the aboveproblems and as a result, found that when a benzoylpyridine derivativerepresented by the formula (I) given hereinafter and a specificfungicide are used in combination, an unexpectedly excellent fungicidaleffect can be obtained as compared with a case where the respectivecompounds are used alone.

Namely, the present invention provides a fungicidal compositioncontaining as active ingredients (a) a benzoylpyridine derivativerepresented by the formula (I) or its salt:

(wherein X is a halogen atom, a nitro group, a substitutable hydrocarbongroup, a substitutable alkoxy group, a substitutable aryloxy group, asubstitutable cycloalkoxy group, a hydroxyl group, a substitutablealkylthio group, a cyano group, a carboxyl group which may be esterifiedor amidated, or a substitutable amino group, n is 1, 2, 3 or 4; R¹ is asubstitutable alkyl group, R^(2′) is a substitutable alkyl group, asubstitutable alkoxy group, a substitutable aryloxy group, asubstitutable cycloalkoxy group or a hydroxyl group, p is 1, 2 or 3, andR^(2″) is a substitutable alkoxy group or a hydroxyl group, providedthat at least two of R^(2′) and R^(2″) may form a condensed ringcontaining an oxygen atom) and (b) at least one fungicide selected fromthe group consisting of a strobilurin compound, an azole compound, amorpholine compound, a pyrimidinamine compound, a guanidine compound, anorganic chlorine compound, an imidazole compound, an antibiotic, apyridinamine compound, a quinoxaline compound, a dithiocarbamatecompound, a cyanoacetamide compound, a phenylamide compound, a sulfenicacid compound, a copper compound, an isoxazole compound, anorganophosphorus compound, a N-halogenothioalkyl compound, adicarboxyimide compound, a benzanilide compound, piperazine compound, apyridine compound, a carbinol compound, a piperidine compound, anorganotin compound, an urea compound, a cynnamic acid compound, a phenylcarbamate compound, a cyanopyrrole compound, an oxazolidinone compound,a thiazole carboxyamide compound, a silyl amide compound, an aminoacidamidecarbamate compound, an imidazolidine compound, a hydroxyanilidecompound, an oxime ether compound, a phenoxyamide compound, abenzophenone compound, Isoprothiolane, Pyroquilon, Dichlomezine,Quinoxyfen, Propamocarb Hydrochloride, Chloropicrin, Dazomet,Metam-sodium, Nicobifen, Diclocymet and Proquinazid. The presentinvention further provides a method for controlling plant diseases,which comprises applying the above fungicidal composition to plants.

In the formula (I), the halogen atom is fluorine, chlorine, bromine oriodine, and it may, for example, be preferably fluorine, chlorine orbromine.

The hydrocarbon moiety in the substitutable hydrocarbon group in theformula (I) may, for example, be a C₁₋₆ alkyl (such as methyl, ethyl,propyl, isopropyl, butyl, isobutyl or t-butyl), a C₂₋₆ alkenyl (such asvinyl, allyl, isopropenyl or 3-methyl-2-butenyl), a C₂₋₆ alkynyl (suchas ethynyl, 1-propynyl or 2-propynyl), a C₃₋₆ cycloalkyl (such ascyclopropyl, cyclopentyl or cyclohexyl) or a C₆₋₁₀ aryl. Further, thesecondary substituent in the substitutable hydrocarbon group may, forexample, be the same or different one to five substituents selected fromthe group consisting of aryl, aryloxy, hydroxy, nitro, nitroxy, halogen(such as fluorine, chlorine, bromine or iodine), haloalkoxy (such as aC₁₋₄ haloalkoxy, for instance CF₃O or HCF₂O), cycloalkyl, amino,alkylthio and cyano. Among these substitutable hydrocarbon groups, asubstitutable alkyl group is preferred, and an alkyl group isparticularly preferred. Further, among alkyl groups, a C₁₋₄ alkyl groupis most preferred.

The alkyl moiety in the substitutable alkyl group, the substitutablealkoxy group and the substitutable alkylthio group in the formula (I) ispreferably a C₁₋₆ alkyl (such as methyl, ethyl, propyl, isopropyl,butyl, isobutyl or t-butyl), particularly preferably a C₁₋₄ alkyl.Further, the secondary substituent in these substituents may be the sameor different one to five substituents selected from the group consistingof aryl, aryloxy, hydroxy, nitro, nitroxy, halogen (such as fluorine,chlorine, bromine or iodine), haloalkoxy (such as a C₁₋₄ haloalkoxy, forinstance CF₃O or HCF₂O), cycloalkyl, amino, alkylthio and cyano. Amongsuch substituents having an alkyl moiety, a non-substituted substituentis preferred, a C₁₋₄ alkyl is particularly preferred, and methyl is mostpreferred.

The aryl moiety in the substitutable aryloxy group in the formula (I)may be phenyl, or a condensed polycyclic group such as naphthyl, but itis preferably phenyl. Further, the secondary substituent, for instancesubstitutable group may, for example, be halogen, alkyl, alkoxy orhydroxy.

The cycloalkyl moiety in the substitutable cycloalkoxy group in theformula (I) consists of three to ten carbons, and it may, for example,be a monocyclic group such as cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl or cyclooctyl, or a condensed polycyclic group, but it ispreferably a monocyclic group. Further, the secondary substituent inthese substitutable groups may, for example, be halogen, alkyl, alkoxyor hydroxy. Among the cycloalkoxy moieties, cyclohexyloxy is mostpreferred.

The carboxyl group which may be esterified or amidated in the formula(I) may, for example, be a carboxyl group which may be esterified, suchas a C₁₋₆ alkoxycarbonyl group (such as a methoxycarbonyl group, anethoxycarbonyl group, a propoxycarbonyl group, an isopropoxycarbonylgroup, a butoxycarbonyl group, an isobutoxycarbonyl group or at-butoxycarbonyl group), a nitroxy C₁₋₄ alkoxyaminocarbonyl group (suchas a 2-nitroxyethoxycarbonyl group or a 3-nitroxypropoxycarbonyl group)or a phenyl C₁₋₄ alkoxycarbonyl group (such as a benzyloxycarbonyl groupor a phenethyloxycarbonyl group); or a carboxyl group which may beamidated, such as a carbamoyl group, a C₁₋₆ monoalkylaminocarbonyl group(such as a methylaminocarbonyl group, an ethyaminocarbonyl group, apropylaminocarbonyl group, an isopropylaminocarbonyl group, abutylaminocarbonyl group, an isobutylaminocarbonyl group or at-butylaminocarbonyl group), a di C₁₋₆ alkylaminocarbonyl group (such asa dimethylaminocarbonyl group, a diethylaminocarbonyl group, adipropylaminocarbonyl group, a diisopropylaminocarbonyl group, adibutylaminocarbonyl group or an isodibutylaminocarbonyl group), anitroxy C₁₋₄ alkylaminocarbonyl group (such as a2-nitroxyethylaminocarbonyl group or a 3-nitroxypropylaminocarbonylgroup), a phenyl C₁₋₄ alkylaminocarbonyl group (such as abenzylaminocarbonyl group or a phenethylaminocarbonyl group), a C₃₋₆cycloalkylaminocarbonyl group (such as a cyclopropylaminocarbonyl group,a cyclopentylaminocarbonyl group or a cyclohexylaminocarbonyl group), acyclic aminocarbonyl group (such as a morpholinocarbonyl group, apiperidinocarbonyl group, a pyrrolidinocarbonyl group or athiomorpholinocarbonyl group) or an aminocarbonyl group.

The substitutable amino group in the formula (I) may, for example, be anamino group; or an alkylamino group such as a monoalkylamino group or adialkylamino group. The alkyl moiety in the alkylamino group ispreferably a C₁₋₄ alkyl. Further, the secondary substituent in thesubstitutable amino group may be the same or different one to fivesubstituents selected from aryl, aryloxy, hydroxy, nitro, nitroxy,halogen (such as fluorine, chlorine, bromine or iodine), haloalkoxy(such as a C₁₋₄ haloalkoxy group, for instance CF₃O or HCF₂O),cycloalkyl, amino, alkylthio and cyano.

In the above secondary substituents in the above-mentioned respectivesubstituents, the aryl moiety, the cycloalkyl moiety and the alkylmoiety are as defined for the respective substituents.

The compound represented by the formula (I) may form a salt togetherwith an acidic substance, and it may form, for example, an inorganicacid salt such as a hydrochloride, a hydrobromide, a phosphate, asulfate or a nitrate; or an organic acid salt such as an acetate, abenzoate, a p-toluenesulfonate, a methanesulfonate or apropanesulfonate.

The compounds represented by the formula (I) may be prepared by aproduction process as disclosed in WO02/2527. Further, they may beproduced also by a method in accordance with Journal of OrganicChemistry, 58, 7832 (1993), European Journal of Organic Chemistry, 7,1371-1376 (2001) or Preparation Examples given hereinafter.

The strobilurin compound may, for example, be Kresoxim-Methyl,Azoxystrobin, Metominofen, Trifloxystrobin, Picoxystrobin, Oryzastrobin,Dimoxystrobin or Fluoxastrobin. Among them, Kresoxim-Methyl andAzoxystrobin are preferred.

Kresoxim-Methyl is a compound disclosed in The Pesticide Manual (TwelfthEdition, BRITISH CROP PROTECTION COUNCIL), p. 568-569. Further,Azoxystrobin is a compound disclosed in The Pesticide Manual (TwelfthEdition, BRITISH CROP PROTECTION COUNCIL), p. 54-55.

The azole compound may, for example, be Epoxiconazole, Triflumizole,Oxpoconazole fumarate, Tebuconazole, Imibenconazole, Tetraconazole,Triadimefon, Bitertanol, Etaconazole, Propiconazole, Penconazole,Flusilazole, Myclobutanil, Cyproconazole, Hexaconazole, Furconazole-cis,Prochloraz, Metconazole, Sipconazole, Prothioconazole, Simeconazole,Tricyclazole, Probenazole, Fluquinconazole or Triadimenol. Among them,Epoxiconazole, Triflumizole, oxpoconazole fumarate, Tebuconazole,Imibenconazole, Tetraconazole, Cyproconazole, Metconazole,Fluquinconazole and Triadimenol are preferred.

Epoxiconazole is a compound disclosed in The Pesticide Manual (TwelfthEdition, BRITISH CROP PROTECTION COUNCIL), p. 349-350. Triflumizole is acompound disclosed in The Pesticide Manual (Twelfth Edition, BRITISHCROP PROTECTION COUNCIL), p. 940-941. Oxpoconazole fumarate is acompound disclosed in The Pesticide Manual (Twelfth Edition, BRITISHCROP PROTECTION COUNCIL), p. 699. Tebuconazole is a compound disclosedin The Pesticide Manual (Twelfth Edition, BRITISH CROP PROTECTIONCOUNCIL), p. 864-865. Imibenconazole is a compound disclosed in ThePesticide Manual (Twelfth Edition, BRITISH CROP PROTECTION COUNCIL), p.535-536. Tetraconazole is a compound disclosed in The Pesticide Manual(Thirteenth Edition, BRITISH CROP PROTECTION COUNCIL), p. 945-946.Cyproconazole is a compound disclosed in The Pesticide Manual(Thirteenth Edition, BRITISH CROP PROTECTION COUNCIL), p. 248-249.Metconazole is a compound disclosed in The Pesticide Manual (ThirteenthEdition, BRITISH CROP PROTECTION COUNCIL), p. 643-644. Fluquinconazoleis a compound disclosed in The Pesticide Manual (Thirteenth Edition,BRITISH CROP PROTECTION COUNCIL), p. 472-473. Triadimenol is a compounddisclosed in The Pesticide Manual (Thirteenth Edition, BRITISH CROPPROTECTION COUNCIL), p. 987-989.

The morpholine compound may, for example, be Fenpropimorph orSpiroxamine. Fenpropimorph is a compound disclosed in The PesticideManual (Twelfth Edition, BRITISH CROP PROTECTION COUNCIL), p. 399-400.Spiroxamine is a compound disclosed in The Pesticide Manual (TwelfthEdition, BRITISH CROP PROTECTION COUNCIL), p. 842-843.

The pyrimidinamine compound may, for example, be Mepanipyrim,Pyrimethanil or Cyprodinil. Among them, Mepanipyrim is preferred.Mepanipyrim is a compound disclosed in The Pesticide Manual (TwelfthEdition, BRITISH CROP PROTECTION COUNCIL), p. 596-597.

The guanidine compound may, for example, be Iminoctadine. Iminoctadineis a compound disclosed in The Pesticide Manual (Twelfth Edition,BRITISH CROP PROTECTION COUNCIL), p. 539-541.

The organic chlorine compound may, for example, be Chlorothalonil,Fthalide or Quintozene. Among them, Chlorothalonil is preferred.Chlorothalonil is a compound disclosed in The Pesticide Manual (TwelfthEdition, BRITISH CROP PROTECTION COUNCIL), p. 168-169.

The imidazole compound may be Cyazofamid, Benomyl, Thiophanate-Methyl orCarbendazim. Among them, Cyazofamid is preferred. Cyazofamid is acompound disclosed in The Pesticide Manual (Twelfth Edition, BRITISHCROP PROTECTION COUNCIL), p. 523-524.

The antibiotic may, for example, be Polyoxins. Polyoxins is a compounddisclosed in The Pesticide Manual (Twelfth Edition, BRITISH CROPPROTECTION COUNCIL), p. 752-754.

The pyridinamine compound may, for example, be Fluazinam.

The quinoxaline compound may, for example, be Quinomethionate.

The dithiocarbamate compound may, for example, be Maneb, Zineb,Mancozeb, Polycarbamate, Metiram or Propineb.

The cyanoacetamide compound may, for example, be Cymoxanil.

The phenylamide compound may, for example, be Metalaxyl, Metalaxyl M,Oxadixyl, Ofurace, Benalaxyl, Furalaxyl or Cyprofuram.

The sulfenic acid compound may, for example, be Dichlofluanid.

The copper compound may, for example, be Cupric hydroxide or OxineCopper.

The isoxazole compound may, for example, be Hymexazol.

The organophosphorus compound may, for example, be Fosetyl-Al,Tolcofos-Methyl, S-benzyl O,O-diisopropylphosphorothioate, O-ethylS,S-diphenylphosphorodithioate or aluminum ethyl hydrogen S phosphonate.

The N-halogenothioalkyl compound may, for example, be Captan, Captafolor Folpet.

The dicarboxyimide compound may, for example, be Procymidone, Iprodioneor Vinclozolin.

The benzanilide compound may, for example, be Flutolanil, Mepronil,Zoxamid or Tiadinil.

The piperazine compound may, for example, be Triforine.

The pyridine compound may, for example, be Pyrifenox.

The carbinol compound may, for example, be Fenarimol or Flutriafol.

The piperidine compound may, for example, be Fenpropidine. Fenpropidineis a compound disclosed in The Pesticide Manual (Thirteenth Edition,BRITISH CROP PROTECTION COUNCIL), p. 419-420.

The organotin compound may, for example, be Fentin Hydroxide or FentinAcetate.

The urea compound may, for example, be Pencycuron.

The cinnamic acid compound may, for example, be Dimethomorph orFlumorph.

The phenyl carbamate compound may, for example, be Diethofencarb.

The cyanopyrrole compound may, for example, be Fludioxonil orFenpiclonil.

The oxazolidinone compound may, for example, be Famoxadone.

The thiazole carboxamide compound may, for example, be Ethaboxam.

The silyl amide compound may, for example, be Silthiopham.

The aminoacid amidecarbamate compound may, for example, be Iprovalicarbor Benthiavalicarb.

The imidazolidine compound may, for example, be Fenamidone.

The hydroxyanilide compound may, for example, be Fenhexamid.

The benzene sulfonamide compound may, for example, be Flusulfamid.

The oxime ether compound may, for example, be Cyflufenamid.

The phenoxyamide compound may, for example, be Fenoxanil.

The benzophenone compound may, for example, be Metrafenone. Metrafenoneis a compound disclosed in AG CHEM NEW COMPOUND REVIEW, VOLUME 21, 2003,p. 17.

Another compound may, for example, be Isoprothiolane, Pyroquilon,Diclomezine, Quinoxyfen, Propamocarb Hydrochloride, Chloropicrin,Dazomet, Metam-sodium, Nicobifen, Diclocymet or Proquinazid.

The fungicide (b) as an active ingredient in the fungicidal compositionof the present invention may be the above-mentioned compounds. Amongthem, it is preferred to use at least one member selected from the groupconsisting of the strobilurin compound, the azole compound, themorpholine compound, the pyrimidinamine compound, the guanidinecompound, the organic chlorine compound, the imidazole compound, theantibiotic, the piperidine compound and the benzophenone compound. It ismore preferred to use at least one member selected from the groupconsisting of Kresoxim-Methyl, Azoxystrobin, Epoxiconazole,Triflumizole, Oxpoconazole fumarate, Tebuconazole, Imibenconazole,Tetraconazole, Cyproconazole, Metconazole, Fluquinconazole, Triadimenol,Fenpropimorph, Spiroxamine, Mepanipyrim, Iminoctadine, Chlorothalonil,Cyazofamid, Polyoxins, Fenpropidine and Metrafenone.

EFFECTS OF THE IVNENTION

The fungicidal composition of the present invention has stable and highfungicidal effects against cultivated crops infected with plantdiseases, and it is possible to control the plant diseases by thiscomposition.

BEST MODE FOR CARRYING OUT THE INVENTION

Preferred processes for production of the compound of the above formula(I) or its salt will be exemplified below.

(1) A process for producing a compound of the above formula (I) or itssalt by reacting a substituted benzaldehyde represented by the formula(VI-1):

(wherein R¹, R^(2′), R^(2″) and p are as defined above) with a metalsalt of a substituted pyridine derivative represented by the formula(VII-1):

(wherein X is as defined above, and Z is a metal atom or its complexsalt) to produce phenylpyridylmethanol represented by the formula (X):

(wherein X, R¹, R^(2′), R^(2″), n and p are as defined above), andoxidizing it.

(2) A process for producing a compound of the above formula (I) or itssalt by reacting a metal salt of a substituted benzene derivativerepresented by the formula (VI-2):

(wherein R¹, R², R^(2″) and p are as defined above, and Z is a metalatom or its complex salt) with a substituted pyridylaldehyde representedby the formula (VII-2):

(wherein X and n are as defined above) to produce phenylpyridylmethanolrepresented by the formula (X), and oxidizing it.

In the above Production Processes (1) and (2), the metal atomrepresented by Z may, for example, be a typical metal atom such aslithium, magnesium, zinc or copper; or a transition metal atom such aspalladium or ruthenium. Further, it may be a composite salt of a metalatom (ate complex) such as lithium diaryl cuprate or lithium triarylcuprate instead of the metal atom.

The compounds of the above formulae (VI-1) and (VII-2) can be producedusually in accordance with a known method such as a method disclosed inJournal of Organic Chemistry, vol. 57, p. 6,847 to 6, 852, 1992.

The phenylpyridylmethanol represented by the formula (X) to be producedby the above Production Processes (1) and (2) is oxidized by knownprocedures such as a metal oxidizing agent such as manganese dioxide orchromic acid, swern oxidation method (dimethyl sulfoxide and oxalylchloride) or ruthenium oxidation method (tetrapropylammoniumperruthenate and N-methyl morpholine-N-oxide) and converted into thecompound represented by the formula (I).

The compound of the formula (VII-1) in Production Process (1) can beobtained by reacting a compound represented by the formula (VIII):

(wherein X and n are as defined above, and Hal is a halogen atom) with acompound represented by the formula (IX): Ar-Z (wherein Ar is an alkylgroup or an aryl group, and Z is as defined above) This reaction iscarried out preferably in the presence of a solvent at a reactiontemperature of from −100° C to 120° C. Further, Ar-Z may, for example,be isopropylmagnesium chloride, isopropylmagnesium bromide,methyllithium, butyllithium, phenyllithium or diisopropylmagnesium.Otherwise, it may be obtained by a hydrogen-metal exchange reactionusing a metal amide such as lithium diisopropylamide or lithium2,2,6,6-tetramethylpiperazide.

(3) A process for producing a compound of the above formula (I) or itssalt by reacting a compound of the above formula (VIII) with a compoundrepresented by the formula (XI):

(wherein R¹, R^(2′), R^(2″) and p are as defined above, and M is a metalatom) in the presence of a transition metal catalyst under carbonmonoxide atmosphere.

In the above Production Process (3), the metal atom may, for example, behydroxyboron, alkylboron, alkoxyboron, magnesium halide, zinc halide,alkyltin, alkylsilane or alkoxysilane. Further, the transition metalcatalyst may, for example, be palladium, rhodium or ruthenium. Thisreaction is carried out preferably in the presence of a single or mixedinert solvent at a reaction temperature of from 0° C. to 200° C.Further, this reaction must be carried out in a carbon monoxideatmosphere under normal pressure or under a pressurized state by carbonmonoxide using a pressure resistant reaction apparatus.

(4) A process for producing a compound of the above formula (I) or itssalt by reacting a compound of the above formula (VII-1) with a compoundrepresented by the formula (XII):

(wherein R¹, R^(2′), R^(2″) and p are as defined above, and Y is aleaving group).

In the above Production Process (4), the leaving group represented by Ymay, for example, be halogen, cyano or alkoxy. This reaction is carriedout preferably in the presence of a single or mixed inert solventselected from aliphatic hydrocarbons such as hexane, cyclohexane andoctane; and ether solvents such as diisopropyl ether, tetrahydrofuranand dimethoxyethane at a reaction temperature of from −100° C. to 120°C. Further, it is possible to accelerate the reaction by using atransition metal complex of e.g. nickel, palladium or iron as acatalyst.

(5) A process for producing a compound of the above formula (I) or itssalt by reacting a compound represented by the formula (XIII):

(wherein X and n are as defined above) with a compound represented bythe formula (XIV):

(wherein R¹, R^(2′), R^(2″) and p are as defined above) in the presenceof a Lewis acid or a dehydrating agent.

The reaction in Production Process (5) is carried out preferably in thepresence of a solvent at a reaction temperature of from 0° C. to 200° C.The Lewis acid or the dehydrating agent may, for example, be P₂O₅,phosphorus oxychloride, polyphosphoric acid, sulfuric acid ordicyclohexylcarbodiimide (DCC). Further, the solvent may be any solventso long as it is not involved in the reaction, and it may, for example,be a halogenated hydrocarbon such as 1,2-dichloroethane or methylenechloride, an aromatic hydrocarbon such as benzene, chlorobenzene,dichlorobenzene or nitrobenzene, or a mixture thereof.

(6) A process for producing a compound of the above formula (I) or itssalt, comprising a first step (a) of reacting a compound of the aboveformula (XIII) with a halogenating agent to obtain a compoundrepresented by the formula (XV):

(wherein X and n are as define above, and Hal is a halogen atom) and asecond step (b) of subjecting the compound of the formula (XV) obtainedin the first step and a compound of the above formula (XIV) toFriedel-Crafts reaction to obtain the compound of the above formula (I).

To the reaction in the first step of Production Process (6), a usualacid halogenating reaction may be applied. This reaction is carried outpreferably in the presence or absence of an inert solvent at a reactiontemperature of from 0 to 200° C. The halogenating agent to be used inthis reaction may, for example, be a fluorinating agent, a chlorinatingagent or a brominating agent, and it is preferably a chlorinating agentsuch as thionyl chloride, phosphorus oxychloride or oxalyl chloride. TheFriedel-Crafts reaction in the second step of Production Process (6) maybe carried out in the presence of a catalyst in a solvent or withoutsolvent at a reaction temperature of from −78° C to 200° C., and it iscarried out preferably at a reaction temperature of from 0° C. to 100°C. The catalyst to be used in the reaction may, for example, be a Lewisacid catalyst such as FeCl₃, AlCl₃, SnCl₄, ZnCl₂, TiCl₄, SbCl₅, BF₃ orBiCl₃, trifluoromethanesulfonic acid or graphite. Further, the solventis an inert solvent under reaction conditions and it may, for example,be 1,2-dichloroethane, methylene chloride, chlorobenzene,dichlorobenzene or nitrobenzene, or a mixture thereof. Further, theproduct may be produced by synthesis or derivatizing with reference toFriedel-Crafts Chemistry (Olah, G.A.).

The compound of the above formula (XIII) to be used as a startingmaterial for production in Production Processes (5) and (6) may beobtained by oxidizing a compound of the above formula (VII-2). Theoxidizing agent may be an inorganic or organic oxidizing agent which iscommonly used. Otherwise, it may be obtained by reacting a compound ofthe above formula (VII-1) directly with dry ice or by reacting it withethyl chlorocarbonate, followed by hydrolysis. Otherwise, the productmay be produced by synthesis or derivatizing from a substitutedpyridinecarboxylic acid or its derivative by a known method fromliterature, e.g. with reference to J. Heterocyclic. Chem., 36, 653(1999). Further, the product may be produced by synthesis orderivatizing with reference to “Experimental Chemistry 22, OrganicSyntheses IV, 1992”, fourth edition, The Chemical Society of Japan.

Among benzoylpyridine derivatives represented by the formula (I),preferred is a compound represented by the formula (I′):

(wherein when A is —N═, B is —CX⁴═; when A is —CH═, B is —N═; each of X¹and X² which are independent of each other, is a halogen atom, an alkoxygroup, a hydroxyl group, an alkyl group, a CF₃ group or an alkylthiogroup; X³ is a hydrogen atom, a halogen atom, an alkoxy group, an alkylgroup, a CF₃ group or an alkylthio group; X⁴ is a hydrogen atom, ahalogen atom, an alkoxy group, an alkyl group, a CF₃ group or analkylthio group; R¹ is an alkyl group; R^(2′) is an alkoxy group; p is1, 2 or 3; and each of R^(2″) and R^(2′″) is an alkoxy group).

The compound represented by the above formula (I′) may be a compoundwherein A is —CH═ and B is —N═ i.e. a compound represented by theformula (I′-1):

(wherein X¹, X², X³, R¹, R^(2′), R^(2″) and R^(2′″) are as definedabove), and a compound wherein A is —N═ and B is —CX⁴═ i.e. a compoundrepresented by the formula (I′-2):

(wherein X¹, X², X³, X⁴, R¹, R², R³ and R^(2′″) are as defined above).

Among compounds represented by the above formula (I′-1), it is preferredto use at least one compound selected from the group consisting of3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-bromo-5-chloro-2-methoxypyridine(Compound No. 1),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-4-ethyl-2-methoxypyridine(Compound No. 2),3-(4,5-dimethoxy-2-methylbenzoyl)-4,5-dichloro-2-methoxypyridine(Compound No. 3),3-(5-ethoxy-4-methoxy-2-methylbenzoyl)-4,5-dichloro-2-methoxypyridine(Compound No. 4),3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-bromo-5-chloro-2-ethoxypyridine(Compound No. 5),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-ethoxy-4-methylpyridine(Compound No. 6),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-bromo-4-chloro-2-ethoxypyridine(Compound No. 7),3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-chloro-5-iodo-2-methoxypyridine(Compound No. 8),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-iodo-2,4-dimethoxypyridine(Compound No. 9),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylthiopyridine(Compound No. 10),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2,4-dimethoxypyridine(Compound No. 11),3-(2,3,4-trimethoxy-6-methylbenzoyl)-4,5-dibromo-2-methoxypyridine(Compound No. 12),3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-bromo-2-methoxy-5-methylpyridine(Compound No. 13),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-bromo-4-trifluoromethyl-2-methoxypyridine(Compound No. 14),3-(2,3,4-trimethoxy-6-methylbenzoyl)-4,5-dichloro-2-methoxypyridine(Compound No. 15),3-(2,3,4-trimethoxy-6-methylbenzoyl)-2,4-dichloro-5-methylpyridine(Compound No. 16),3-(2,3,4-trimethoxy-6-methylbenzoyl)-2,4-dichloro-5-iodopyridine(Compound No. 17),3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-fluoro-4-iodo-5-methylpyridine(Compound No. 18),3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-fluoro-4,5-dimethylpyridine(Compound No. 19),3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-methoxy-4,5-dimethylpyridine(Compounds No. 20),3-(2-ethoxy-3,4-dimethoxy-6-methylbenzoyl)-2-ethoxy-4,5-dimethylpyridine(Compound No. 21),3-(2,3,4-trimethoxy-6-methylbenzoyl)-4,5-dimethyl-2-methylthiopyridine(Compound No. 22),3-(2,3,4-trimethoxy-6-methylbenzoyl)-S-bromo-4-chloro-2-methoxypyridine(Compound No. 23),3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-chloro-2-methoxy-5-methylpyridine(Compound No. 24),3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-chloro-5-trifluoromethyl-4-methylpyridine(Compound No. 25),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-trifluoromethyl-2-methoxy-4-methylpyridine(Compound No. 26),3-(2,3,4-trimethoxy-6-methylbenzoyl)-2,4-dichloro-5-trifluoromethylpyridine(Compound No. 27),3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-chloro-5-trifluoromethyl-2-methoxypyridine(Compound No. 28),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-4-ethynyl-2-methoxypyridine(Compound No. 29),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-4-fluoromethyl-2-methoxypyridine(Compound No. 30),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-bromo-4-fluoromethyl-2-methoxypyridine(Compound No. 31),3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-fluoromethyl-2-methoxy-5-methylpyridine(Compound No. 32),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-4-difluoromethyl-2-methoxypyridine(Compound No. 33),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-ethyl-4-trifluoromethyl-2-methoxypyridine(Compound No. 34),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine(Compound No. 35),3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-bromo-2-methoxy-4-methylpyridine(Compound No. 36),3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-trifluoromethyl-2-methoxy-5-methylpyridine(Compound No. 37) and3-(4,5-dimethoxy-2-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine(Compound No. 38).

Among compounds represented by the above formula (I′-2), it is preferredto use at least one compound selected from the group consisting of4-(2,3,4-trimethoxy-6-methylbenzoyl)-2,5-dichloro-3-trifluoromethylpyridine(Compound No. 39),4-(2,3,4-trimethoxy-6-methylbenzoyl)-2-chloro-3-trifluoromethyl-5-methoxypyridine(Compound No. 40),4-(2,3,4-trimethoxy-6-methylbenzoyl)-2-bromo-3-trifluoromethyl-5-methoxypyridine(Compound No. 41),4-(2,3,4-trimethoxy-6-methylbenzoyl)-2,3,5-trichloropyridine (CompoundNo. 42), 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3,5-dichloropyridine(Compound No. 43),4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-chloro-5-methoxypyridine(Compound No. 44),4-(2,3,4-trimethoxy-6-methylbenzoyl)-2-bromo-3-chloro-5-methoxypyridine(Compound No. 45) and4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-bromo-5-methylpyridine (CompoundNo. 46).

The fungicidal composition of the present invention is usefulparticularly as an agricultural and horticultural fungicide. As theagricultural and horticultural fungicide, it is effective forcontrolling diseases such as blast, brown spot or sheath blight of rice(Oryza sativa, etc.); powdery mildew, scab, rust, snow mold, snowblight, loose smut, eye spot, leaf spot or glume blotch of cereals(Hordeum vulgare, Tricum aestivum, etc.); melanose or scab of citrus(Citrus spp., etc.); blossom blight, powdery mildew, Alternaria leafspot or scab of apple (Malus pumila); scab or black spot of pear (Pyrusserotina, Pyrus ussuriensis, Pyrus communis); brown rot, scab orPhomopsis rot of peach (Prunus persica, etc.); anthracnose, ripe rot,powdery mildew or downy mildew of grape (Vitis vinifera spp., etc.);anthracnose or brown stem rot of Japanese persimmon (Diospyros kaki,etc.); anthracnose, powdery mildew, gummy stem blight or downy mildew ofcucurbit (Cucumis melo, etc.); early blight, leaf mold or late blight oftomato (Lycopersicon esculentum); various Alternaria disease pathogensof cruciferous vegetables (Brassica sp., Raphanus sp., etc); late blightor early blight of potato (Solanum tuberosum); powdery mildew ofstrawberry (Fragaria, etc.); and gray mold or disease caused bySclerotinia of various crops. It is particularly effective againstpowdery mildew of cereals and vegetables and blast of rice. Further, itis effective also for controlling soil diseases caused by plantpathogens such as Fusarium, Pythium, Rhizoctonia, Verticillium andPlasmodiophora.

The plurality of the active ingredients constituting the fungicidalcomposition of the present invention are, in the same manner asconventional agricultural chemicals, mixed with various adjuvants andformulated into various formulations such as a dust, granules,water-dispersible granules, a wettable powder, a water-based suspensionconcentrate, an oil-based suspension concentrate, water solublegranules, an emulsifiable concentrate, a soluble concentrate, a paste,an aerosol and an ultra low-volume formulation. However, so long as thepurpose of the present invention can be accomplished, any type offormulation which is commonly used in this field is applicable. Suchadjuvants include solid carriers such as diatomaceous earth, slakedlime, calcium carbonate, talc, white carbon, kaoline, bentonite, amixture of kaolinite and sericite, clay, sodium carbonate, sodiumbicarbonate, mirabilite, zeolite and starch; solvents such as water,toluene, xylene, solvent naphtha, dioxane, acetone, isophorone, methylisobutyl ketone, chlorobenzene, cyclohexane, dimethyl sulfoxide,dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone andalcohol; anionic surfactants and spreaders such as a salt of fatty acid,a benzoate, an alkylsulfosuccinate, a dialkylsulfosuccinate, apolycarboxylate, a salt of alkylsulfuric acid ester, an alkyl sulfate,an alkylaryl sulfate, an alkyl diglycol ether sulfate, a salt of alcoholsulfuric acid ester, an alkyl sulfonate, an alkylaryl sulfonate, an arylsulfonate, a lignin sulfonate, an alkyldiphenyl ether disulfonate, apolystyrene sulfonate, a salt of alkylphosphoric acid ester, analkylaryl phosphate, a styrylaryl phosphate, a salt of polyoxyethylenealkyl ether sulfuric acid ester, a polyoxyethylene alkylaryl ethersulfate, a salt of polyoxyethylene alkylaryl ether sulfuric acid ester,a polyoxyethylene alkyl ether phosphate, a salt of polyoxyethylenealkylaryl phosphoric acid ester, and a salt of a condensate ofnaphthalene sulfonate with formalin; nonionic surfactants and spreaderssuch as a sorbitan fatty acid ester, a glycerin fatty acid ester, afatty acid polyglyceride, a fatty acid alcohol polyglycol ether,acetylene glycol, acetylene alcohol, an oxyalkylene block polymer, apolyoxyethylene alkyl ether, a polyoxyethylene alkylaryl ether, apolyoxyethylene styrylaryl ether, a polyoxyethylene glycol alkyl ether,a polyoxyethylene fatty acid ester, a polyoxyethylene sorbitan fattyacid ester, a polyoxyethylene glycerin fatty acid ester, apolyoxyethylene hydrogenated castor oil, and a polyoxypropylene fattyacid ester; and vegetable and mineral oils such as olive oil, kapok oil,castor oil, palm oil, camellia oil, coconut oil, sesame oil, corn oil,rice bran oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil,linseed oil, tung oil, and liquid paraffins. Such adjuvants may beselected from known components so long as the purpose of the presentinvention can thereby be accomplished. Further, various additives whichare commonly used, such as a filler, a thickener, an anti-settlingagent, an anti-freezing agent, a dispersion stabilizer, a phytotoxicityreducing agent, and an anti-mold agent, may also be employed. The blendratio of the active ingredient components to the various adjuvants isusually from 0.005:99.995 to 95:5, preferably from 0.2:99.8 to 90:10. Inthe actual application of such a formulation, it may be used as it is,or may be diluted to a predetermined concentration with a diluent suchas water, and various spreaders may be added thereto, as the caserequires.

A method for controlling plant diseases, which comprises applying thefungicidal composition of the present invention to agricultural andhorticultural plants, is also included in the present invention. Theconcentration of the fungicidal composition of the present invention cannot generally be defined, as it varies depending upon the crop plants tobe treated, the application method, the type of the formulation, thedose, etc. However, it is applied in a concentration of the activeingredients being usually from 0.1 to 10,000 ppm, preferably from 1 to2,000 ppm in the case of foliage treatment, and usually from 10 to100,000 g/ha, preferably from 200 to 20,000 g/ha in the case of soiltreatment.

The formulation containing the fungicidal composition of the presentinvention or a diluted product thereof may be applied by an applicationmethod which is commonly used, such as spreading (spreading, spraying,misting, atomizing, grain diffusing or application on water surface),soil application (such as mixing or irrigation) or surface application(such as coating, dust coating or covering). Further, it may be appliedalso by so-called ultra low volume. In this method, the formulation maycontain 100% of the active ingredient.

In the fungicidal composition of the present invention, the appropriatemixing weight ratio of the benzoylpyridine derivative represented by theformula (I) or its salt to another fungicide is usually from 1:10,000 to10,000:1, preferably from 1:1,000 to 1,000:1, more preferably from 1:200to 200:1.

EXAMPLES

Now, the present invention will be described in further detail withreference to Examples. However, it should be understood that the presentinvention is by no means restricted thereto.

Preparation Example 1

Preparation of3-(2,3,4-trimethoxy-6-methylbenzoyl)-4,5-dichloro-2-methoxypyridine(Compound No. 15) (a) 222 ml of n-butyllithium (1.57 mo/l hexanesolution) was dropwise added at −20° C. to a solution having 34.2 g (340mmol) of diisopropylamine dissolved in 400 ml of tetrahydrofuran,followed by stirring for 1 hour. The solution was cooled to −78° C., anda solution having 32.0 g (330 mmol) of 2-fluoropyridine dissolved in 50ml of tetrahydrofuran was added, followed by stirring for 4 hours toprepare 2-fluoro-3-pyridyllithium. Then, to this solution, a solutionhaving 87.1 g (341 mmol) of iodine dissolved in 150 ml oftetrahydrofuran was added, followed by stirring for 1 hour. 200 ml ofwater was added to the mixture to terminate the reaction, andtetrahydrofuran was distilled off under reduced pressure. Afterextraction with ethyl ether, the organic layer was dried over sodiumsulfate and subjected to filtration, and the solvent was distilled offunder reduced pressure to obtain 67.4 g (crude yield: 92%) of crude2-fluoro-3-iodopyridine.

¹H-NMR(CDC₁ ₃, 400 MHz): (ppm)=6.91-6.88(m,1H), 8.08-8.12(m,2H)

(b) 189 ml of n-butyllithium (1.57 mol/l hexane solution) was dropwiseadded at −20° C. to a solution having 30.2 g (302 mmol) ofdiisopropylamine dissolved in 380 ml of tetrahydrofuran, followed bystirring for 1 hour. The solution was cooled to −78° C., and a solutionhaving 67.4 g (302 mmol) of crude 2-fluoro-3-iodopyridine obtained inStep (a) dissolved in 100 ml of tetrahydrofuran was added, followed bystirring for 1 hour, so that 2-fluoro-3-iodo-4-pyridyllithium formed atthe initial stage was isomerized to 2-fluoro-4-iodo-3-pyridyllithium.300 ml of water was added to the reaction mixture to terminate thereaction, and tetrahydrofuran was distilled off under reduced pressure.After extraction with ethyl ether, the organic layer was dried oversodium sulfate and subjected to filtration, and the solvent wasdistilled off under reduced pressure to obtain 59.3 g (crude yield: 89%)of crude 2-fluoro-4-iodopyridine.

¹H-NMR (CDCl₃, 400 MHz): δ (ppm)=7.33(d,1H, J=2.8 Hz), 7.51(d,1H, J=5.2Hz), 7.88(dd,1H, J=5.2 Hz, 2.8 Hz)

(c) 500 ml of methanol was added to 59.4 g (253 mmol) of crude2-fluoro-4-iodopyridine obtained in Step (b) so that it was dissolved inmethanol, and 21.5 g (398 mmol) of sodium methoxide was added, followedby reflux with heating for 3 hours. 300 ml of water was added toterminate the reaction, and methanol was distilled off under reducedpressure. After extraction with ethyl ether, the organic layer was driedover sodium sulfate and subjected to filtration, and the solvent wasdistilled off under reduced pressure to obtain 56.7 g (crude yield: 91%)of crude 4-iodo-2-methoxypyridine.

¹H-NMR(CDCl₃, 400 MHz): δ (ppm)=3.86(s,3H), 7.12-7.16(m,2H), 7.79(d,1H,J=5.6 Hz)

(d) 50.6 ml (2 mol/l tetrahydrofuran solution) of isopropylmagnesiumchloride was cooled with ice, and a solution having 19.8 g (84.3 mmol)of crude 4-iodo-2-methoxypyridine obtained in Step (c) dissolved in 80ml of tetrahydrofuran was added, followed by stirring at 0° C. for 1hour and then at room temperature for 1 hour to prepare2-methoxy-4-pyridylmagnesium chloride. Then, 16.9 g (127 mmol) ofN-chlorosuccinimide was gradually added, followed by stirring at roomtemperature for 1 hour. 100 ml of water was added to terminate thereaction, and tetrahydrofuran was distilled off under reduced pressure.After extraction with ethyl ether, the organic layer was dried oversodium sulfate and subjected to filtration, and the solvent wasdistilled off under reduced pressure to obtain 11.0 g (crude yield: 91%)of crude 4-chloro-2-methoxypyridine.

¹H-NMR(CDCl₃, 400 MHz): δ (ppm)=3.91(s, 3H), 6.70(d, 1H, J=2.0 Hz),6.81(dd, 1H, J=6.0 Hz, 2.0 Hz), 7.99(d,1H, J=6.0 Hz)

(e) 10.0 g (69.9 mmol) of crude 4-chloro-2-methoxypyridine obtained inStep (d) was dissolved in 100 ml of dimethylformamide, and 37.2 g (279mmol) of N-chlorosuccinimide was added, followed by stirring at roomtemperature for 12 hours. 400 ml of water was added to terminate thereaction, followed by extraction with ethyl ether. The organic layer waswashed with a saturated sodium chloride solution, dried over sodiumsulfate and subjected to filtration, and the solvent was distilled offunder reduced pressure to obtain 9.10 g (crude yield: 73%) of crude4,5-dichloro-2-methoxypyridine.

¹H-NMR(CDCl₃, 400 MHz): δ (ppm)=3.90(s, 3H), 6.85(s, 1H), 8.14(s, 1H)

(f) 15.1 ml of n-butyllithium (1.57 mol/l hexane solution) was dropwiseadded at −20° C. to a solution having 2.40 g (23.7 mmol) ofdiisopropylamine dissolved in 30 ml of tetrahydrofuran, followed bystirring for 1 hour. The solution was cooled to −78° C., and a solutionhaving 4.22 g (23.6 mmol) of 4,5-dichloro-2-methoxypyridine obtained inStep (e) dissolved in 20 ml of tetrahydrofuran was added, followed bystirring for 2 hours to prepare 4,5-dichloro-2-methoxy-3-pyridyllithium.Then, to this solution, a solution having 5.00 g (23.8 mmol) of2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 20 ml oftetrahydrofuran was added, followed by stirring for 30 minutes. 50 ml ofwater was added to the mixture to terminate the reaction, andtetrahydrofuran was distilled off under reduced pressure. Afterextraction with ethyl ether, the organic layer was dried over sodiumsulfate and subjected to filtration, and the solvent was distilled offunder reduced pressure, followed by purification by silica gel columnchromatography to obtain 4.66 g (yield: 51%) of(2,3,4-trimethoxy-6-methylphenyl)(4,5-dichloro-2-methoxy-3-pyridyl)methanol.

¹H-NMR(CDCl₃, 400 MHz): δ (ppm)=2.32(s, 3H), 3.52(s, 3H), 3.77(s, 3H),3.82(s, 3H), 4.11(s, 3H), 5.32(d, 1H, J=10.0 Hz), 6.21(d, 1H, J=10.0Hz), 6,55(s, 1H), 8.07(s, 1H)

(g) 13.8 g (159 mmol) of manganese dioxide was added to a solutionhaving 4.66 g (12.0 mmol) of (2,3,4-trimethoxy-6-methylphenyl)(4,5-dichloro-2-methoxy-3-pyridyl)methanol obtained in Step (f)dissolved in 30 ml of toluene, followed by reflux with heating for 2hours. After cooling to room temperature, manganese dioxide was removedby filtration on the pad of celite, and toluene was distilled off underreduced pressure, followed by purification by silica gel columnchromatography to obtain 2.98 g (yield : 65%) of3-(2,3,4-trimethoxy-6-methylbenzoyl)-4,5-dichloro-2-methoxypyridine.

¹H-NMR(CDCl₃, 400 MHz): δ (ppm)=2.46(s,3H), 3.45(s,3H), 3.74(s,3H),3.90(s,3H), 4.00(s,3H), 6.55(s,1H), 8.13(s,1H)

Preparation Example 2 Preparation of3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-methoxy-4,5-dimethylpyridine(Compound No. 20)

(a) 26.5 ml of n-butyllithium (1.57 mol/l hexane solution) was dropwiseadded at −78° C. to a solution having 4.02 g (39.8 mmol) ofdiisopropylamine dissolved in 70 ml of tetrahydrofuran, followed bystirring for 30 minutes. To this solution, a solution having 4.42 g(39.8 mmol) of 2-fluoro-5-methylpyridine dissolved in 18 ml oftetrahydrofuran was added, followed by stirring for 4 hours to prepare2-fluoro-5-methyl-3-pyridyllithium. Then, to this solution, a solutionhaving 10.1 g (39.8 mmol) of iodine dissolved in 27 ml oftetrahydrofuran was added, followed by stirring for 2 hours. 16 ml ofwater and 120 ml of a sodium thiosulfate aqueous solution were charged,followed by extraction with ethyl ether. The organic layer was driedover magnesium sulfate and subjected to filtration, the solvent wasdistilled off under reduced pressure, and the obtained crude product waspurified by silica gel chromatography to obtain 3.15 g (yield: 33%) of2-fluoro-3-iodo-5-methylpyridine.

¹H-NMR(CDCl₃, 400 MHz): (ppm)=2.27(s, 3H), 7.95(m, 2H)

(b) 8.90 ml (1.57 mol/l hexane solution) was dropwise added at -78° C.to a solution having 1.34 g (13.3 mmol) of diisopropylamine dissolved in27 ml of tetrahydrofuran, followed by stirring for 30 minutes. To thissolution, a solution having 3.15 g (13.3 mmol) of2-fluoro-3-iodo-5-methylpyridine obtained in Step (a) dissolved in 5 mlof tetrahydrofuran was added, followed by stirring for 1 hour, so that2-fluoro-3-iodo-5-methyl-4-pyridyllithium formed at the initial stagewas isomerized to 2-fluoro-4-iodo-5-methyl-3-pyridyllithium. To thereaction mixture, a solution having 2.79 g (13.3 mmol) of2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 5 ml oftetrahydrofuran was added, followed by stirring for 2 hours. After thetemperature was increased to room temperature, 50 ml of water was added,followed by extraction with ethyl ether. The organic layer was driedover magnesium sulfate and subjected to filtration, the solvent wasdistilled off under reduced pressure, and the obtained crude product waspurified by silica gel chromatography to obtain 4.45 g (yield: 75%) of(2,3,4-trimethoxy-6-methylphenyl)(2-fluoro-4-iodo-5-methyl-3-pyridyl)methanol.

¹H-NMR(CDCl₃, 400 MHz): (ppm)=2.21(s, 3H), 2.42(s, 3H), 3.72(s, 3H),3.79(s, 3H), 3.81(s, 3H), 4.97(d, 1H, J=10.0 Hz), 6.08(d, 1H, J=10.0Hz), 6.46(s, 1H), 7.86(s, 1H)

(c) 17.3 g (0.18 mol) of manganese dioxide was added to a solutionhaving 4.35 g (9.70 mmol) of(2,3,4-trimethoxy-6-methylphenyl)(2-fluoro-4-iodo-5-methyl-3-pyridyl)methanolobtained in Step (b) dissolved in 130 ml of toluene, followed by refluxwith heating for 2 hours. After cooling to room temperature, manganesedioxide was removed by filtration on the pad of celite, and toluene wasdistilled off under reduced pressure, followed by purification by silicagel chromatography to obtain 2.80 g (yield: 65%) of3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-fluoro-4-iodo-5-methylpyridine(Compound No. 18, melting point 140 to 141° C.).

¹H-NMR(CDCl₃, 400 MHz): δ (ppm)=2.41(s, 3H), 2.50(s, 3H), 3.42(s, 3H),3.90(s, 3H), 3.74(s, 3H), 6.57(s, 1H), 7.94(s, 1H)

(d) 1.50 g (3.37 mmol) of3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-fluoro-4-iodo-5-methylpyridineobtained in Step (c), 1.40 g (10.1 mmol) of potassium carbonate, 0.39 g(0.34 mmol) of tetrakis(triphenylphosphine)palladium, 15 ml of dioxaneand 0.42 g (1.67 mmol) of 50% trimethylboroxin were mixed, followed byreflux with heating for 6 hours. After cooling to room temperature,filtration on the pad of celite and washing with ethyl acetate andtetrahydrofuran were carried out, the solvent was distilled off underreduced pressure, and the obtained crude product was purified by silicagel chromatography to obtain 0.79 g (yield: 70%) of3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-fluoro-4,5-dimethylpyridine(Compound No. 19).

¹H-NMR(CDCl₃, 400 MHz): δ (ppm)=2.28(s, 3H), 2.32(s, 3H), 2.42(s, 3H),3.35(s, 3H), 3.74(s, 3H), 3.90(s, 3H), 6.57(s, 1H), 7.94(s, 1H)

(e) A solution having 0.06 g (1.5 mmol) of 60% sodium hydride dissolvedin 1 ml of methanol, was dropwise added to a solution having 0.20 g(0.60 mmol) of3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-fluoro-4,5-dimethylpyridineobtained in Step (d) dissolved in 2.5 ml of methanol, followed by refluxwith heating for 16 hours. After cooling to room temperature, 5 ml ofwater was added, and diluted hydrochloric acid was added to bring thesolution weakly acidic. After extraction with ethyl ether, washing witha sodium chloride solution was carried out, and the organic layer wasdried over magnesium sulfate and subjected to filtration, the solventwas distilled off under reduced pressure, and the obtained crude productwas purified by silica gel chromatography to obtain 89.0 mg (yield: 43%)of 3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-methoxy-4,5-dimethylpyridine.

¹H-NMR(CDCl₃, 400 MHz): δ (ppm)=2.19(s, 3H), 2.21(s, 3H), 2.39(s, 3H),3.24(s, 3H), 3.70(s, 3H), 3.74(s, 3H), 3.87(s, 3H), 6.53(s, 1H), 7.87(s,1H)

Preparation Example 3 Preparation of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-bromo-4-chloro-2-methoxypyridine(Compound No. 23)

(a) 5.76 g (40.1 mmol) of 4-chloro-2-methoxypyridine was dissolved in 20ml of dimethylformamide, and a dimethylformamide (20 ml) solution of8.01 g of N-bromosuccinimide (98%, 44.1 mmol) was dropwise added over aperiod of 30 minutes. After stirring at room temperature for 2 days, anunreacted material was confirmed, and thus 2.85 g of N-bromosuccinimide(98%, 16 mmol) was further added, followed by stirring at roomtemperature further for 3 days. The reaction mixture was poured into 250ml of water, followed by extraction with ethyl ether (100 ml each) threetimes. The organic layer was washed with water (100 ml), a sodiumthiosulfate aqueous solution (100 ml) and then a saturated sodiumchloride solution (100 ml), dried over magnesium sulfate and subjectedto filtration, and the solvent was distilled off under reduced pressure.The obtained crude product was purified by silica gel chromatography toobtain 7.10 g (yield: 80%) of 5-bromo-4-chloro-2-methoxypyridine.

¹H-NMR(CDCl₃, 400MHz): δ (ppm)=3.91 (s,3H), 6.89(s,1H), 8.28(s,1H)

(b) 18.3 ml of n-butyllithium (1.57 mol/l hexane solution, 27 mmol) wasdropwise added at 0° C. to a solution having 3.84 g (27 mmol) of2,2,6,6-tetramethylpiperidine dissolved in 36 ml of tetrahydrofuranunder an argon stream, followed by stirring at 0° C. for 30 minutes. Theobtained solution was cooled to −78° C., and a solution having 6.10 g(27 mmol) of 5-bromo-4-chloro-2-methoxypyridine dissolved in 24 ml oftetrahydrofuran was added, followed by stirring at the same temperaturefor 2 hours to prepare 5-bromo-4-chloro-2-methoxy-3-pyridyllithium.Then, a solution having 5.50 g (26 mmol) of2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 24 ml oftetrahydrofuran was added, followed by stirring at the same temperaturefor 1 hour. To the reaction mixture, 37 ml of a saturated ammoniumchloride aqueous solution and then 150 ml of water were added, and thetemperature was increased to room temperature, followed by extractionwith ethyl acetate (150 ml each) three times. The organic layer waswashed with a saturated sodium chloride solution (100 ml), dried overmagnesium sulfate and subjected to filtration, and the solvent wasdistilled off under reduced pressure. The obtained crude product waspurified by silica gel chromatography to obtain 6.53 g (yield: 56%) of(2,3,4-trimethoxy-6-methylphenyl)(5-bromo-4-chloro-2-methoxy-3-pyridyl)methanol.

¹H-NMR(CDCl₃, 400 MHz): δ (ppm)=2.33(s, 3H), 3.54(s, 3H) 3.79(s,3H),3.84(s,3H), 3.98(s,3H), 5.32(d,1H J=9.6 Hz), 6.23(d,1H J=9.6 Hz),6.49(s,1H), 8.21(s,1H)

4.55 g of manganese dioxide (88%, 46 mmol) was added to a solutionhaving 2.21 g (5.1 mmol) of(2,3,4-trimethoxy-6-methylphenyl)(5-bromo-4-chloro-2-methoxy-3-pyridyl)methanoldissolved in 70 ml of toluene, followed by reflux with heating for 1hour. 4.55 g of manganese dioxide (88%, 46 mmol) was further added,followed by reflux with heating for 1 hours. The reaction mixture wascooled to room temperature, manganese dioxide was removed by filtrationon the pad of celite, and toluene was distilled off under reducedpressure. The obtained crude product was purified by silica gelchromatography to obtain 1.90 g (yield: 87%) of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-bromo-4-chloro-2-methoxypyridine(melting point 84 to 87° C).

¹H-NMR(CDCl₃, 400 MHz): δ (ppm)=2.48(s,3H), 3.45(s,3H), 3.75(s,3H),3.87(s,3H), 3.91(s,3H), 6.57(s,1H), 8.27(s,1H)

Preparation Example 4 Preparation of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine(Compound No. 35)

(a) 9.2 g (69 mmol) of N-chlorosuccinimide was charged to aN,N-dimethylformamide (DMF) 15 ml solution of 8.0 g (65 mmol) of2-methoxy-4-methylpyridine, followed by stirring for 18 hours. Water wasadded to the reaction solution, and the aqueous layer was extracted withdiethyl ether. The organic layer was washed with a saturated sodiumchloride solution, dried over anhydrous sodium sulfate and subjected tofiltration, and the solvent was distilled off under reduced pressure.The crude product was purified by silica gel column chromatography toobtain 8.5 g (yield: 82%) of 5-chloro-2-methoxy-4-methylpyridine(melting point 32 to 33° C.).

¹HNMR(CDCl₃, 300 MHz): 2.32(s, 3H), 3.89(s, 3H), 6.62 (s, 1H), 8.05(s,1H)

(b) 20.2 g (114 mmol) of N-bromosuccinimide was charged to aN,N-dimethylformamide (DMF) 15 ml solution of 7.2 g (46 mmol) of5-chloro-2-methoxy-4-methylpyridine, followed by stirring at 50° C. for20 hours. A diluted sodium thiosulfate aqueous solution was added to thereaction solution, and the aqueous layer was extracted with diethylether. The organic layer was washed with a saturated sodium chloridesolution, dried over anhydrous sodium sulfate and subjected tofiltration on the pad of a silica gel cake, and the solvent wasdistilled off under reduced pressure to obtain 10.6 g (yield: 97%) of3-bromo-5-chloro-2-methoxy-4-methylpyridine (melting point: 44 to 45°C.).

¹HNMR(CDCl₃, 300 MHz): δ2.51(s, 3H), 3.98 (s, 3H), 8.01 (s, 1H)

(c) 4 ml of tetrahydrofuran and 0.62 ml (4.4 mmol) of triethylamine wereadded to 2.2 ml (4.4 mmol) of isopropylmagnesium chloride (2.0 mol/ltetrahydrofuran solution), the mixture was cooled to 0° C., and asolution having 1.0 g (4.2 mmol) of3-bromo-5-chloro-2-methoxy-4-methylpyridine dissolved in 5 ml oftetrahydrofuran was dropwise added, followed by stirring for 3 hours toprepare 5-chloro-2-methoxy-4-methyl-3-pyridylmagnesium chloride. Asolution having 0.89 g (4.2 mmol) of2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 5 ml oftetrahydrofuran was dropwise added to the reaction solution, followed bystirring for 1 hour, and then the temperature was increased to roomtemperature, followed by stirring further for 1 hour. Water was added tothe reaction solution to terminate the reaction, followed by extractionwith ethyl acetate. The organic layer was washed with a saturated sodiumchloride solution, dried over anhydrous magnesium sulfate and subjectedto filtration, and the solvent was distilled off under reduced pressure.The crude product was purified by silica gel column chromatography toobtain 1.1 g (yield: 70%) of(2,3,4-trimethoxy-6-methylphenyl)(5-chloro-2-methoxy-4-methyl-3-pyridyl)methanol(pale yellow oily substance).

¹HNMR(CDCl₃, 300 MHz): δ2.26(s, 3H), 2.27(s, 3H), 3.54(s, 3H), 3.80(s,3H), 3.84(s, 3H), 3.94(s, 3H), 5.32(d, 1H, J=9.0 Hz), 6.12(d, 1H, J=9.0Hz), 6.47(s, 1H), 8.02(s, 1H)

(d) 4 g of active manganese dioxide was added to a toluene 15 mlsolution of 0.64 g (1.7 mmol) of(2,3,4-trimethoxy-6-methylphenyl)(5-chloro-2-methoxy-4-methyl-3-pyridyl)methanol,followed by stirring under reflux with heating for 1 hour. The reactionsolution was subjected to filtration on the pad of celite, and thesolvent was distilled off under reduced pressure to obtain 0.57 g(yield: 90%) of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine(melting point 94.5 to 95.5° C.)

¹HNMR(CDCl₃, 300 MHz): 2.31(s, 3H), 2.40(s, 3H), 3.30(s, 3H), 3.73(s,3H), 3.74(s, 3H), 3.88(s, 3H), 6.54(s, 1H), 8.06(s, 1H)

Preparation Example 5 Preparation of3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-trifluoromethyl-2-methoxy-5-methylpyridine(Compound No. 37)

(a) A solution having 5.05 g (27.8 mmol) of2-chloro-4-trifluoromethylpyridine and 3.59 g (66.5 mmol) of sodiummethoxide dissolved in 40 ml of methanol was stirred under reflux withheating for 4 hours. Water was added to terminate the reaction, followedby extraction with diethyl ether. The organic layer was dried overanhydrous sodium sulfate and subjected to filtration on the pad of asilica gel cake. The solvent was distilled off under reduced pressure toobtain 4.19 g (yield: 85%) of 4-trifluoromethyl-2-methoxypyridine.

¹H-NMR(CDCl₃, 400 MHz): δ (ppm)=3.96(s, 3H), 6.95(s, 1H), 7.05(d, 1H,J=5.2 Hz), 8.29(d, 1H, J=5.2 Hz)

(b) 4.00 ml (78.1 mmol) of bromine was dropwise added to a solutionhaving 8.21 g (46.4 mmol) of 4-trifluoromethyl-2-methoxypyridineobtained in Step (a) and 7.98 g (97.3 mmol) of sodium acetate dissolvedin 15 ml of acetic acid, followed by stirring for 4 days. A potassiumhydroxide aqueous solution was added to terminate the reaction, followedby extraction with diethyl ether. The organic layer was dried overanhydrous sodium sulfate and subjected to filtration on the pad of asilica gel cake. The solvent was distilled off under reduced pressure toobtain 5.81 g of a mixture of5-bromo-4-trifluoromethyl-2-methoxypyridine and the starting material4-trifluoromethyl-2-methoxypyridine (molar ratio 55:45).

¹H-NMR(CDCl₃, 400 MHz): δ (ppm)=3.94(s, 3H), 7.03(s, 1H), 8.37(s, 1H)

(c) 17.1 ml of n-butyllithium (1.57 mol/l hexane solution) was dropwiseadded at 0° C. to a solution having 3.80 ml (27.1 mmol) ofdiisopropylamine dissolved in 50 ml of tetrahydrofuran, followed bystirring for 30 minutes. The solution was cooled to −78° C., and asolution having 5.81 g of the mixture of5-bromo-4-trifluoromethyl-2-methoxypyridine and4-trifluoromethyl-2-methoxypyridine (molar ratio 55:45) obtained in Step(c) dissolved in 10 ml of tetrahydrofuran was added, followed bystirring for 45 minutes to prepare a mixture of5-bromo-4-trifluoromethyl-2-methoxy-3-pyridyllithium and4-trifluoromethyl-2-methoxy-3-pyridyllithium. A solution having 5.51 g(26.2 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 15 mlof tetrahydrofuran was added, followed by stirring for 1 hour. Water wasadded to the mixture to terminate the reaction, and tetrahydrofuran wasdistilled off under reduced pressure. After extraction with ethylacetate, the organic layer was dried over anhydrous sodium sulfate andsubjected to filtration, and the solvent was distilled off under reducedpressure. The crude product was purified by silica gel columnchromatography to obtain 5.02 g of(2,3,4-trimethoxy-6-methylphenyl)(5-bromo-4-trifluoromethyl-2-methoxy-3-pyridyl)methanol.

¹H-NMR(CDCl₃, 400 MHz): δ (ppm)=2.35(s, 3H), 3.29(s, 3H), 3.74(s, 3H),3.82(s, 3H), 3.92(s, 3H), 4.87(d, 1H, J=10.8 Hz), 6.21(d, 1H, J=10.8Hz), 6.51(s, 1H), 8.31(s, 1H)

(d) 20.0 g (230 mmol) of manganese dioxide was added to a solutionhaving 4.80 g (10.3 mmol) of(2,3,4-trimethoxy-6-methylphenyl)(5-bromo-4-trifluoromethyl-2-methoxy-3-pyridyl)methanolobtained in Step (c) dissolved in 110 ml of toluene, followed bystirring under reflux with heating for 1 hour. After cooling to roomtemperature, the mixture was subjected to filtration on the pad ofcelite and the solvent was distilled off under reduced pressure. Thecrude product was purified by silica gel column chromatography to obtain3.93 g (yield: 82%) of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-bromo-4-trifluoromethyl-2-methoxypyridine(Compound No. 31).

¹H-NMR(CDCl₃, 400 MHz): δ (ppm)=2.57(s, 3H), 3.36(s, 3H), 3.75(s, 3H),3.86(s, 3H), 3.93(s, 3H), 6.59(s, 1H), 8.38(s, 1H)

(e) 3.80 ml (3.80 mmol) of dimethylzinc (1.0 mol/l hexane solution) wasdropwise added at 0° C. to a solution having 0.60 g (1.29 mmol) of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-bromo-4-trifluoromethyl-2-methoxypyridineobtained in Step (d) and 0.10 g (0.09 mmol) oftetrakis(triphenylphosphine)palladium dissolved in 10 ml oftetrahydrofuran, and the temperature was increased naturally, followedby stirring at room temperature for 8 days. Water was added to terminatethe reaction, and tetrahydrofuran was distilled off under reducedpressure. After extraction with ethyl acetate, the organic layer wasdried over anhydrous sodium sulfate and subjected to filtration, and thesolvent was distilled off under reduced pressure. The crude product waspurified by silica gel column chromatography to obtain 0.50 g (yield:96%) of3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-trifluoromethyl-2-methoxy-5-methylpyridine.

¹H-NMR(CDCl₃, 400 MHz): (ppm)=2.41(s, 3H), 2.56(s, 3H), 3.29(s, 3H),3.74(s, 3H), 3.83(s, 3H), 3.91(s, 3H), 6.58(s, 1H), 8.05(s, 1H)

Preparation Example 6 Preparation of4-(2,3,4-trimethoxy-6-methylbenzoyl)-2,5-dichloro-3-trifluoromethylpyridine(Compound No. 39)

(a) 17 ml (25 mmol) of n-butyllithium (1.5 mol/l hexane solution) wasdropwise added at 0° C. to a solution having 3.6 ml (25 mmol) ofdiisopropylamine dissolved in 60 ml of diethyl ether, followed bystirring for 45 minutes. The solution was cooled to −78° C., and asolution having 6.0 g (24 mmol) of2,3,6-trichloro-5-trifluoromethylpyridine dissolved in 8 ml of diethylether was added, followed by stirring for 25 minutes to prepare2,3,6-trichloro-5-trifluoromethyl-4-pyridyllithium, and then a solutionhaving 5.0 g (24 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehydedissolved in 12 ml of toluene was added, followed by stirring for 1hour. 30 ml of water was added to the mixture to terminate the reaction,and the aqueous layer was extracted with ethyl acetate. Then, theorganic layer was dried over anhydrous sodium sulfate and subjected tofiltration, and the solvent was distilled off under reduced pressure toobtain(2,3,4-trimethoxy-6-methylphenyl)(2,3,6-trichloro-5-trifluoromethyl-4-pyridyl)methanol(melting point 131 to 135° C.).

(b) 2.7 ml (19 mmol) of triethylamine and 0.9 g of 5% palladium carbonwere added to a solution having2,3,4-trimethoxy-6-methylphenyl)(2,3,6-trichloro-5-trifluoromethyl-4-pyridyl)methanolobtained in Step (a) dissolved in 200 ml of methanol, followed bystirring under a hydrogen atmosphere for 14 hours. The mixture wassubjected to filtration, 30 ml of water was added, and methanol wasdistilled off under reduced pressure. After extraction with ethylacetate, the organic layer was dried over anhydrous sodium sulfate andsubjected to filtration, and the solvent was distilled off under reducedpressure. The crude product was purified by silica gel columnchromatography to obtain 2.38 g (yield: 24%) of(2,3,4-trimethoxy-6-methylphenyl)(2,5-dichloro-3-trifluoromethyl-4-pyridyl)methanol(melting point 162 to 165° C.)

(c) 14 g of manganese dioxide was added to a solution having 3.5 g (8.2mmol) of(2,3,4-trimethoxy-6-methylphenyl)(2,5-dichloro-3-trifluoromethyl-4-pyridyl)methanolobtained in Step (b) dissolved in 100 ml of toluene, followed bystirring under reflux with heating for 6 hours. The mixture was cooledand then subjected to filtration, and toluene was distilled off underreduced pressure. The crude product was purified by silica gel columnchromatography to obtain 3.1 g (yield: 89%) of4-(2,3,4-trimethoxy-6-methylbenzoyl)-2,5-dichloro-3-trifluoromethylpyridine(melting point 106 to 109° C.)

Preparation Example 7 Preparation of4-(2,3,4-trimethoxy-6-methylbenzoyl)-2-chloro-3-trifluoromethyl-5-methoxypyridine(Compound No. 40)

(a) 70.0 ml (106 mmol) of n-butyllithium (1.5 mol/l hexane solution) wasdropwise added at 0° C. to a diethyl ether 120 ml solution of 15.0 ml(107 mmol) of diisopropylamine, followed by stirring for 1 hour. Thesolution was cooled to −78° C., and a diethyl ether 10 ml solution of22.1 g (102 mmol) of 2,3-dichloro-5-trifluoromethylpyridine was added,followed by stirring for 30 minutes to prepare2,3-dichloro-5-trifluoromethyl-4-pyridyllithium, and then a toluene 40ml solution of 21.0 g (100 mmol) of2,3,4-trimethoxy-6-methylbenzaldehyde was added, followed by stirringfor 2 hours. 30 ml of water was added to the mixture to terminate thereaction, and the aqueous layer was extracted with ethyl acetate. Then,the organic layer was dried over anhydrous sodium sulfate and subjectedto filtration, and the solvent was distilled off under reduced pressure.The crude product was purified by silica gel column chromatography toobtain 24.8 g (yield: 58%) of(2,3,4-trimethoxy-6-methylphenyl)(2,3-dichloro-5-trifluoromethyl-4-pyridyl)methanol(melting point 95 to 98° C.).

(b) 2.1 g of 5% palladium carbon was added to a methanol 200 ml solutionof 24.8 g (58.1 mmol) of(2,3,4-trimethoxy-6-methylphenyl)(2,3-dichloro-5-trifluoromethyl-4-pyridyl)methanolobtained in Step (a) and 9.50 ml (68.2 mmol) of triethylamine, followedby stirring under hydrogen atmosphere for 4 hours. The mixture wassubjected to filtration, 50 ml of water was added, and methanol wasdistilled off under reduced pressure. The aqueous layer was extractedwith ethyl acetate, and the organic layer was dried over anhydroussodium sulfate and subjected to filtration, and the solvent wasdistilled off under reduced pressure. The crude product was purified bysilica gel column chromatography to obtain 15.9 g (yield: 70%) of(2,3,4-trimethoxy-6-methylphenyl)(3-chloro-5-trifluoromethyl-4-pyridyl)methanol (melting point: 102 to105° C.).

(c) 45 g of manganese dioxide was added to a toluene 220 ml solution of15.9 g (40.6 mmol) of (2,3,4-trimethoxy-6-methylphenyl)(3-chloro-5-trifluoromethyl-4-pyridyl)methanol obtained in Step (b),followed by stirring under reflux with heating for 2 hours. The mixturewas subjected to filtration, and the solvent was distilled off underreduced pressure to obtain 14.9 g (yield: 94%) of4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-chloro-5-trifluoromethylpyridine.

(d) 16.4 g (304 mmol) of sodium methoxide was added to a toluene 150 mlsolution of 18.5 g (47.5 mmol) of4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-chloro-5-trifluoromethylpyridineobtained in Step (c) and 16.6 ml (95.4 mmol) of hexamethylphosphoroustriamide, followed by stirring under reflux with heating for 30 minutes.Water was added to terminate the reaction, and the aqueous layer wasextracted with ethyl acetate. Then, the organic layer was dried overanhydrous sodium sulfate and subjected to filtration, and the solventwas distilled off under reduced pressure. The crude product was purifiedby silica gel column chromatography to obtain 11.7 g (yield: 64%) of4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-methoxy-5-trifluoromethylpyridine(melting point: 103 to 106° C.).

(e) 6.1 g (28 mmol) of m-chloroperbenzoic acid (m-CPBA) was added at 0°C. to a chloroform 100 ml solution of 5.6 g (15 mmol) of4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-methoxy-5-trifluoromethylpyridine(Compound No. 122), followed by stirring at room temperature for 18hours. The reaction solution was washed with a sodium hydroxide aqueoussolution, and the solvent was distilled off under reduced pressure toobtain 5.8 g (yield: 99%) of4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-methoxy-5-trifluoromethylpyridine-N-oxide(melting point 128 to 134° C.)

(f) 1.8 ml (19 mmol) of phosphorus oxychloride was added at 0° C. to 4ml of toluene and 8 ml of dimethylformamide, followed by stirring for 10minutes, and then 4.0 g (10 mmol) of4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-methoxy-5-trifluoromethylpyridine-N-oxidewas added, followed by stirring for 20 minutes. After stirring at roomtemperature for 2 hours, the reaction solution was charged into icewater to terminate the reaction. The aqueous layer was extracted withethyl acetate, and then the organic layer was dried over anhydroussodium sulfate and subjected to filtration, and the solvent wasdistilled off under reduced pressure. The crude product was purified bysilica gel column chromatography to obtain 3.57 g (yield: 85%) of4-(2,3,4-trimethoxy-6-methylbenzoyl)-2-chloro-3-trifluoromethyl-5-methoxypyridine(melting point 117 to 119° C.).

Preparation Example 8 Preparation of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine(Compound No. 35)

(a) 45.6 g (217 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde wasdissolved in 130 ml of dimethyl sulfoxide, and an aqueous solution (50ml) of 5.2 g (44 mmol) of sodium dihydrogen phosphate was dropwise addedover a period of 20 minutes. Then, an aqueous solution (180 ml) of 28 g(305 mmol) of sodium chlorite was dropwise added over a period of 3hours, followed by stirring for 2 hours. A saturated sodiumhydrogencarbonate aqueous solution was added until no bubbling occurred,followed by stirring for 1 hour. Then, the reaction solution was washedwith 50 ml of ethyl acetate twice, and concentrated hydrochloric acidwas added to make the aqueous layer acidic, followed by extraction withethyl acetate. The organic layer was washed with a saturated sodiumchloride solution, dried over anhydrous sodium sulfate and subjected tofiltration, and the solvent was distilled off under reduced pressure.The obtained crystals were washed with hexane to obtain 45.6 g (yield:93%) of 2,3,4-trimethoxy-6-methylbenzoic acid (melting point 95 to 97°C.)

¹HNMR: 62.56(s, 3H), 3.86(s, 3H), 3.91(s, 3H), 4.03(s, 3H), 6.60(s, 1H)

(b-1) 6.8 ml (13.6 mmol) of isopropylmagnesium chloride (2Mtetrahydrofuran solution) was cooled to 0° C., and a solution having 1.6g (6.6 mmol) of 3-bromo-5-chloro-2-methoxy-4-methylpyridine dissolved in5 ml of tetrahydrofuran was dropwise added, followed by stirring at thesame temperature for 3 hours to prepare5-chloro-2-methoxy-4-methyl-3-pyridylmagnesium chloride. The reactionsolution was cooled to −78° C., and a solution having 1.2 g (13.3 mmol)of copper(I) cyanide and 1.15 g (27.1 mmol) of lithium chloridedissolved in 15 ml of tetrahydrofuran was dropwise added to prepare a5-chloro-2-methoxy-4-methyl-3-pyridylcopper reagent. Separately, 3.2 g(14.3 mmol) of 2,3,4-trimethoxy-6-methylbenzoic acid prepared in Step(a) was subjected to reflux with heating in 7 ml of thionyl chloride for3 hours, and the surplus thionyl chloride was distilled off underreduced pressure to prepare 2,3,4-trimethoxy-6-methylbenzoyl chloride,which was dissolved in 7 ml of tetrahydrofuran. The solution thusprepared was dropwise added at −78° C. to the above preparedpyridylcopper reagent, followed by stirring for 1 hour, and thetemperature was increased to room temperature, followed by stirringfurther for 2 hours. Water and ammonia water were added to the reactionsolution to terminate the reaction, followed by extraction with ethylacetate. The organic layer was dried over anhydrous magnesium sulfateand subjected to filtration, and the solvent was distilled off underreduced pressure. The crude product was purified by silica gel columnchromatography to obtain 2.6 g (yield: 57%) of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine(melting point 85 to 88° C.), and the compound was identified by ¹HNMR.

(b-2) The same reaction as in Step (b-i) was carried out that 11 ml(11.0 mmol) of an isopropylmagnesium chloride 1M tetrahydrofuransolution and 2.5 g (10.6 mmol) of3-bromo-5-chloro-2-methoxy-4-methylpyridine were used, except that 1.25g (1.1 mmol) of tetrakistriphenylphosphine palladium was used instead ofthe tetrahydrofuran solution of copper(I) cyanide and lithium chloride,and that 2,3,4-trimethoxy-6-methylbenzoyl chloride prepared from 2.4 g(10.6 mmol) of 2,3,4-trimethoxy-6-methylbenzoic acid and 5 ml of thionylchloride was dropwise added at 0° C. over a period of 2 hours, followedby stirring at the same temperature for 15 hours to obtain 1.7 g (yield:43%) of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine,and the compound was identified by ¹HNMR.

(b-3) The same operation as in Step (b-2) was carried out except that 22ml (22.0 mmol) of an isopropylmagnesium chloride 0.5M tetrahydrofuransolution was used instead of the isopropylmagnesium chloride 1Mtetrahydrofuran solution, and 1.14 g (11.5 mmol) of copper chloride wasused instead of tetrakistriphenylphosphine palladium to obtain 1.7 g(yield: 43%) of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine,and the compound was identified by ¹HNMR.

Preparation Example 9 Preparation of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine(Compound No. 35)

(a) A solution having 5.0 g (19 mmol) of 2-bromo-3,4,5-trimethoxytoluenedissolved in 50 ml of diethyl ether was cooled to −78° C., and 15 ml (24mmol) of n-butyllithium (1.6M hexane solution) was dropwise added,followed by stirring for 1.5 hours to form2,3,4-trimethoxy-6-methyl-2-phenyllithium, and then 4.9 ml (43 mmol) oftrimethyl borate was dropwise added, followed by stirring further for 1hour. Diluted sulfuric acid was added to terminate the reaction,followed by stirring for 30 minutes, and water was further added. Theaqueous layer was extracted with ethyl acetate, and the organic layerwas washed with a saturated sodium chloride solution, dried overanhydrous magnesium sulfate and subjected to filtration, and the solventwas distilled off under reduced pressure to obtain 3.26 g (yield: 75%)of 2,3,4-trimethoxy-6-methylphenylboronic acid (melting point 99 to 102°C.).

¹HNMR: δ2.52(s, 3H), 3.83(s, 3H), 3.88(s, 3H), 3.94(s, 3H), 6.56(s, 1H)

(b) 1.0 g (4.3 mmol) of 3-bromo-5-chloro-2-methoxy-4-methylpyridine, 1.2g (5.4 mmol) of 2,3,4-trimethoxy-6-methylphenylboronic acid, 1.8 g (13mmol) of potassium carbonate, 46 mg (0.26 mmol) of palladium chloride,147 mg (0.52 mmol) of tricyclohexylphosphine and 40 ml oftetrahydrofuran were put in a 200 ml autoclave, and carbon monoxide gaswas injected to a pressure of 10 atm, followed by stirring at 120° C.for 20 hours. The reaction solution was subjected to filtration on thepad of celite, water was added, and tetrahydrofuran was distilled offunder reduced pressure. The aqueous solution was extracted with ethylacetate, the organic layer was dried over anhydrous magnesium sulfateand subjected to filtration, and the solvent was distilled off underreduced pressure. The crude product was purified by silica gel columnchromatography to obtain 0.31 g (yield: 20%) of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine(melting point 92 to 94° C.), and the compound was identified by ¹HNMR.

Preparation Example 10 Preparation of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine(Compound No. 35)

(a) Into a 500 ml four-necked flask equipped with a stirrer, acondenser, a thermometer and a nitrogen balloon, 5.4 g (222 mmol) ofmagnesium and 95 ml of tetrahydrofuran were charged, and 17.3 g (220mmol) of isopropyl chloride was dropwise added while keeping thetemperature in the system at 40° C., followed by stirring overnight.Then, while keeping the temperature in the system at 0° C. or below, atetrahydrofuran 95 ml solution of 47.3 g (200 mmol) of3-bromo-5-chloro-2-methoxy-4-methylpyridine was dropwise added, followedby stirring for 3 hours, and the reaction solution was dropwise added todry ice.

The reaction solution was poured into 300 ml of water, the organic layerwas separated out, and a hydrochloric acid solution was dropwise addedto the aqueous layer to make it acidic, followed by extraction withdiethyl ether. The solvent was distilled off under reduced pressure toobtain 26 g (yield: 65%) of 5-chloro-2-methoxy-4-methylnicotinic acid(melting point 127 to 129° C.).

(b) Into a 50 ml four-necked flask equipped with a stirred, a condenser,a thermometer and a nitrogen balloon, 1.0 g (4.96 mmol) of5-chloro-2-methoxy-4-methylnicotinic acid, 0.9 g (4.94 mmol) of3,4,5-trimethoxytoluene, 20 ml of 1,2-dichloroethane and 7.1 g (50.0mmol) of phosphorus pentoxide were charged, followed by stirring underreflux for 1 hour.

The reaction solution was charged into 50 ml of water, and a sodiumhydroxide aqueous solution was added to make the reaction solutionalkaline, the aqueous layer was separated out, and the solvent wasdistilled off under reduced pressure. 5 ml of hexane was added to theobtained residue, and the precipitated crystals were subjected tofiltration to obtain 0.4 g (yield: 22%) of a desired product.

Preparation Example 11 Preparation of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine(Compound No. 35)

Into a 20 ml recovery flask equipped with a reflux condenser, 1.0 g (5.0mmol) of 5-chloro-2-methoxy-4-methylnicotinic acid, 10 g of1,2-dichloroethane and 0.62 g (5.0 mmol) of oxalyl chloride werecharged, followed by stirring at 25° C. for 20 minutes, and the mixturewas heated at from 60° C. to 65° C. for 2 hours. After the reactionmixture was cooled to 25° C., 0.80 g (4.4 mmol) of3,4,5-trimethoxytoluene and 0.70 g (5.2 mmol) of anhydrous aluminumchloride were added to the reaction mixture, followed by stirring at 25°C. for 3 hours.

Water and ethyl acetate were added to the reaction mixture, followed byextraction and liquid-liquid separation, and then the organic layer wasdried over sodium sulfate and the solvent was distilled off underreduced pressure. n-Hexane was added to the precipitated solid, followedby filtration and drying to obtain 0.66 g (yield: 36.1%) of a desiredproduct.

Preparation Example 12 Preparation of3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine(Compound No. 35)

(a) 10 ml of thionyl chloride was added to 6.0 g (26.6 mmol) of2,3,4-trimethoxy-6-methylbenzoic acid, followed by stirring under refluxwith heating for 4 hours, and the surplus thionyl chloride was distilledoff under reduced pressure. 20 ml of toluene, 8 ml of acetonitrile and3.1 g (34.5 mmol) of copper(I) cyanide were added, followed by stirringunder reflux with heating for 16 hours. After cooling to roomtemperature, the reaction solution was subjected to filtration on thepad of celite, and the solvent was distilled off under reduced pressure.The crude product was purified by silica gel column chromatography toobtain 2.8 g (yield: 45%) of 2,3,4-trimethoxy-6-methylbenzoyl cyanide.

¹HNMR: 62.44(s, 3H), 3.85 (s, 3H), 3.95(s, 3H), 4.14(s, 3H), 6.53 (s,1H)

(b) A solution having 1.9 g (8.0 mmol) of2,3,4-trimethoxy-6-methylbenzoyl cyanide dissolved in 20 ml oftetrahydrofuran was cooled to −10° C., and 0.32 g (0.91 mmol) ofiron(III) acetylacetonate were added, followed by stirring for 20minutes. In another reactor, 4 ml of tetrahydrofuran was added to 4.1 ml(8.2 mmol) of an isopropylmagnesium chloride 2M tetrahydrofuran solutionand the mixture was cooled to 0° C., and a solution having 1.0 g (4.2mmol) of 3-bromo-5-chloro-2-methoxy-4-methylpyridine dissolved in 5 mlof tetrahydrofuran was dropwise added, followed by stirring for 3 hoursto form 5-chloro-2-methoxy-4-methyl-3-pyridylmagnesium chloride. Thepyridylmagnesium chloride solution thus prepared was dropwise added tothe above prepared 2,3,4-trimethoxy-6-methylbenzoyl cyanide/iron mixedsolution, followed by stirring for 3 hours. A 10% ammonium chlorideaqueous solution was added to the reaction solution to terminate thereaction, followed by extraction with ethyl acetate. The organic layerwas washed with a saturated sodium chloride solution, dried overanhydrous magnesium sulfate and subjected to filtration, and the solventwas distilled off under reduced pressure. The crude product was purifiedby silica gel column chromatography to obtain 1.7 g (yield: 58%) of adesired product.

Intermediate Preparation Example 1

(a) Into a 2L four-necked flask equipped a stirrer, a thermometer and agas introduction tube (inlet), 324 g (3.00 mol) of2-amino-4-methylpyridine and 485 g of methanol were charged and mixedfor dissolution, and while keeping the temperature in the system at from10 to 30° C., 361.4 g (9.90 mol) of hydrogen chloride gas was introducedover a period of one and a half hours.

Then, in a 2L four-necked flask equipped with a stirrer, a thermometer,a dropping funnel and an introduction tube (outlet) equipped with abubble counter having a gas generation apparatus and a diazotizationapparatus connected, 414 g (6.00 mol) of sodium nitrite, 211 g (6.60mol) of methanol and 454 g of water were mixed, and 812.4 g (3.15 mol)of a 38% sulfuric acid aqueous solution was dropwise added over a periodof 5 hours while keeping the temperature in the system at from 20 to 30°C.

In the methyl nitrite generation apparatus, simultaneously with dropwiseaddition of the 38% sulfuric acid aqueous solution, methyl nitrite gasin an equivalent amount was generated and introduced to thediazotization apparatus through the bubble counter.

Further, for diazotization, the reaction apparatus was cooled with waterso that the temperature in the system would be kept at from 20 to 30° C.

After completion of the introduction of the methyl nitrite gas, stirringwas carried out at the same temperature for 13 hours and the reactionwas completed.

After methanol was distilled off under reduced pressure, 648 g of waterwas charged, and 518 g of a 40% sodium hydroxide aqueous solution wasdropwise added at 30° C. or below to adjust the pH in the system to 12.

The formed oil was extracted with 910 g of diethyl ether, the aqueouslayer was separated out, and the solvent was distilled off under reducedpressure to obtain 375.3 g of an oil. The oil (crude product) had acomposition comprising 70.7% (yield: 69.5%) of2-chloro-4-methylpyridine, 26.6% (yield: 27.2%) of2-methoxy-4-methylpyridine and 2.6% of 2-amino-4-methylpyridine.

(b) Into a 2L four-necked flask equipped with a stirrer, a thermometer,a condenser and a dropping funnel, 356 g of methanol was charged, and237.6 g (4.4 mol) of sodium methoxide was charged with stirring whilekeeping the temperature at 50° C. or below. Then, while keeping thetemperature in the system at from 60 to 70° C., 375.3 g of crude2-chloro-4-methylpyridine (70.7%, 2.2 mol) obtained in the above Stepwas dropwise added over a period of 3 hours.

After completion of the dropwise addition, reflux with heating wascarried out for 3 hours while distilling methanol off (the amount ofmethanol distilled off over 3 hours was 120 g).

After completion of the reaction, methanol remaining in the system wasdistilled off under reduced pressure, and 750 g of water was charged, sothat the inorganic salt was dissolved.

The formed oil was extracted with 1,050 g of diethyl is ether, theaqueous layer was separated out, and the solvent was distilled off underreduced pressure to obtain 370 g of an oil (crude product). The purityof the obtained 2-methoxy-4-methylpyridine was 95% (two step yield from2-amino-4-methylpyridine: 95%).

Intermediate Preparation Example 2 Preparation of5-chloro-4-methyl-2-methoxy-nicotinic acid (a) Preparation of a mixtureof 4,4-dicyano-3-methyl-3-butenal-dimethylacetal and1,1-dicyano-4-methoxy-2-methyl-1,3-butadiene

2.28 g (37 mmol) of acetic acid was added to a toluene 100 ml solutionof 3.15 g (37 mmol) of piperidine, followed by stirring at roomtemperature for 1 hour, and a toluene 20 ml solution of 49.3 g (373mmol) of acetylacetaldehyde dimethyl acetal was added. Further, atoluene 30 ml solution of 24.65 g (373 mmol) of malononitrile was slowlyadded over a period of 20 minutes, followed by stirring at roomtemperature for 5 days. The reaction mixture was washed with 50 ml ofwater and dried over magnesium sulfate, and the solvent was distilledoff under reduced pressure to obtain 69.35 g of a mixture of4,4-dicyano-3-methyl-3-butenol-dimethylacetal and1,1-dicyano-4-methoxy-2-methyl-1,3-butadiene.

(b) Preparation of 3-cyano-4-methylpyridone

(a) 69.35 g of the mixture of4,4-dicyano-3-methyl-3-butenal-dimethylacetal and1,1-dicyano-4-methoxy-2-methyl-1,3-butadiene obtained in Step (a) wasslowly added to 113 g of concentrated sulfuric acid over a period of 3hours so that the temperature would not exceed 30° C. After stirring atroom temperature for 20 minutes, the temperature was increased to 50°C., and stirring was carried out at the same temperature for 2 hours.After the reaction mixture was left to stand to cool, it was slowlypoured into water ice (500 ml), the obtained crystals were collected byfiltration and the crystals were washed with 100 ml of water. Thecrystals were air-dried for 1 week and further dried at 70° C. underreduced pressure for 8 hours to obtain 34.2 g (two step yield: 68%) ofcrude crystals of 3-cyano-4-methylpyridone.

¹H-NMR(400 MHz, DMSO-d6): δ (ppm) 2.35(s,3H), 6.29(d,J=6.4 Hz,1H),7.64(d,J=6.4 Hz,1H)

(c) Preparation of 2-chloro-3-cyano-4-methylpyridine

14 g (104 mmol) of 3-cyano-4-methylpyridone was slowly added to amixture of 6.52 g (31.3 mmol) of phosphorus pentachloride and 30 ml (48g, 313 mmol) of phosphorus oxychloride, followed by stirring at roomtemperature for 70 minutes and then under reflux with heating for 2hours. After the reaction mixture was left to stand to cool, it waspoured into ice water (400 ml) so that the surplus reagent wasdecomposed, followed by extraction with 100 ml of dichloromethane threetimes. The dichloromethane solution was washed with 100 ml of asaturated sodium chloride solution and dried over magnesium sulfate, andthe solvent was distilled off under reduced pressure to obtain 15.1 g ofcrude crystals of 2-chloro-3-cyano-4-methylpyridine. ¹H-NMR(400 MHz,DMSO-d6): δ (ppm) 2.86(s,3H), 7.89(d,J=5.6 Hz,1H), 8.86(d,J=5.6Hz,1H)

(d) Preparation of 3-cyano-4-methyl-2-methoxypyridine

15.1 g of the crude crystals of 2-chloro-3-cyano-4-methylpyridineobtained in (c) was dissolved in 150 ml of anhydrous methanol, and 24.9g (129 mmol) of a methanol solution of 28% sodium methoxide was added,followed by stirring at room temperature for 2 days. The reactionmixture was poured into 200 ml of a saturated sodium chloride solution,followed by extraction with 100 ml of ethyl acetate three times. Theethyl acetate solution was dried over magnesium sulfate and subjected tofiltration through a celite/silica gel column, and the column wassufficiently washed with ethyl acetate. The filtrate and the washingliquid were put together, and the solvent was distilled off underreduced pressure to obtain 14.04 g of crude crystals of3-cyano-4-methyl-2-methoxypyridine.

¹H-NMR(400 MHz, CDCl₃): δ (ppm) 2.51(s,3H), 4.03(s,3H) 6.84(d,J=5.2Hz,1H), 8.18(d,J=5.2 Hz,1H)

(e) Preparation of 5-chloro-3-cyano-4-methyl-2-methoxypyridine

14.04 g (95 mmol) of 3-cyano-4-methyl-2-methoxypyridine obtained in (d)was dissolved in 100 ml is of dimethylformamide, and 25.4 g (190 mmol)of N-chlorosuccinimide was added, followed by stirring at roomtemperature for 3 days. The progress of the reaction was confirmed bythin layer chromatography and as a result, the material was confirmed toremain, and thus stirring was carried out at 50° C. for 22 hours andthen at 60° C. for 22 hours. After the reaction mixture was left tostand to cool, it was poured into 300 ml of water, followed byextraction with 100 ml of ethyl acetate three times. The ethyl acetatesolution was washed with 150 ml of water twice and then 100 ml of asaturated sodium chloride solution in this order, and dried overmagnesium sulfate, and the solvent was distilled off under reducedpressure. The obtained residue was purified by means of a silica gelcolumn to obtain 13.68 g (three step yield: 79%) of5-chloro-3-cyano-4-methyl-2-methoxypyridine. ¹H-NMR (400MHz, CDCl₃): δ(ppm) 2.56(s,3H), 4.03(s,3H) 8.23(s,1H)

(f) Preparation of 5-chloro-3-formyl-4-methyl-2-methoxypyridine

2.47 g (13.5 mmol) of 5-chloro-3-cyano-4-methyl-2-methoxypyridine wasdissolved in 50 ml of anhydrous dichloromethane, the solution was cooledto −78° C., and 20.3 ml (20.3 mmol) of a toluene solution of 1Mdiisobutylammonium hydride was dropwise added slowly. After stirring at−78° C. for two and a half hours, the temperature was graduallyincreased to room temperature, and stirring was carried out at the sametemperature for three days. The obtained solution was cooled in an icebath, and 30 ml of water was slowly added to terminate the reaction. Thereaction mixture was poured into 150 ml of 1N hydrochloric acid,followed by extraction with 100 ml of dichloromethane twice. Thedichloromethane solution was washed with 100 ml of a saturated sodiumchloride solution and dried over magnesium sulfate, and the solvent wasdistilled off under reduced pressure to obtain crude5-chloro-3-formyl-4-methyl-2-methoxypyridine.

¹H-NMR(400 MHz, CDCl₃): δ (ppm) 2.65(s,3H), 4.03(s,3H), 8.25(s,1H),10.48(s,1H)

(g) Preparation of 5-chloro-4-methyl-2-methoxy-nicotinic acid

Crude 5-chloro-3-formyl-4-methyl-2-methoxypyridine obtained in (f) wasdissolved in 14 ml of dimethyl sulfoxide, 5.7 ml of an aqueous solutionof 0.33 g (2.7 mmol) of sodium dihydrogenphosphate, and 20 ml of anaqueous solution of 2.16 g of sodium chlorite (79%, 18.9 mmol) wasfurther dropwise added slowly over a period of 3 hours. The obtainedmixture was stirred at room temperature for 5 days, and 50 ml of asodium bicarbonate aqueous solution was added, followed by stirringovernight. The obtained solution was washed with 50 ml of ethyl acetatetwice, and concentrated hydrochloric acid was added to make the aqueouslayer acidic, followed by extraction with 70 ml of ethyl acetate threetimes. The ethyl acetate solution was washed with 50 ml of a saturatedsodium chloride solution and dried over magnesium sulfate, and thesolvent was distilled off under reduced pressure to obtain crudecrystals. The crude crystals were dissolved in 50 ml of ethyl acetateagain, followed by back extraction with 50 ml of a saturated sodiumbicarbonate aqueous solution twice, and concentrated hydrochloric acidwas added to make the aqueous layer acidic, followed by extraction with70 ml of ethyl acetate three times. The ethyl acetate solution waswashed with 50 ml of a saturated sodium chloride solution and dried overmagnesium sulfate, and the solvent was distilled off under reducedpressure to obtain white crystals. The crystals were washed with 50 mlof hexane and air-dried to obtain 0.55 g (two step yield: 20%) of5-chloro-4-methyl-2-methoxy-nicotinic acid.

¹H-NMR(400 MHz, CDCl₃): δ (ppm) 2.46(s,3H), 3.99(s,3H) 8.16(s,1H)

Now, Test Examples for the present invention will be described. However,it should be understood that the present invention is by no meansrestricted to such specific Examples.

Test Example 1 Test on Preventive Effect Against Wheat Powdery Mildew

Wheat (cultivar: Norin-61-go) was cultivated in a plastic pot having adiameter of 7.5 cm, and when it reached 1.5-leaf stage, 10 ml of achemical solution having each test compound adjusted to a prescribedconcentration, was applied by a spray gun in an amount of 200 L/ha.After the chemical solution dried, conidia of Erysiphe graminis weredusted and inoculated and maintained in a constant temperature chamberat 20° C. From 6 to 8 days after the inoculation, the area ofsporulation was investigated, and the disease rate was determined inaccordance with the following formula, and the results are shown inTables 1 to 53. The average lesion area in the non-treated plot wasdetermined in the same manner as for the treated plot except that waterwas applied by a spray gun instead of the chemical solution.Disease rate=(a/b)×100

-   -   a: average lesion area in the treated plot    -   b: average lesion area in the non-treated plot

Theoretical values were calculated in accordance with the Colby'sformula. The fungicidal composition of 5 the present invention has asynergistic effect regarding the test on preventive effect against wheatpowdery mildew, when the experimental value is lower than thetheoretical value. Theoretical values by the Colby's formula in suchcases are shown in brackets in Tables 1 10 to 53. TABLE 1 Dose of Doseof Compound No. 23 Fenpropimorph 12.5 g/ha 6.3 g/ha 3.1 g/ha 0 g/ha 100g/ha   5(64) 10(80)   80 80 50 g/ha 20(80) 60(100) 65(100) 100 25 g/ha60(80) 80(100) 100 100  0 g/ha 80 100 100

TABLE 2 Dose of Dose of Compound No. 35 Fenpropimorph 6.3 g/ha 3.1 g/ha1.6 g/ha 0 g/ha 100 g/ha 0(1.5) 0(2.3) 2(6.8) 15  0 g/ha 10 15 45

TABLE 3 Dose of Dose of Compound No. 39 Fenpropimorph 12.5 g/ha 6.3 g/ha3.1 g/ha 0 g/ha 100 g/ha 10(28) 7.5(48) 30(48) 80  0 g/ha 35 60 60

TABLE 4 Dose of Dose of Compound No. 40 Fenpropimorph 6.3 g/ha 3.1 g/ha1.6 g/ha 0 g/ha 100 g/ha  2.5(4.5) 2.5(6.7) 5.0(6.7) 15.0 50 g/ha  0(13.5)  2.5(20.2) 17.5(20.2) 45.0 25 g/ha 2.5(30)  5.0(45)  45.0 100 0 g/ha 30.0 45.0 45.0

TABLE 5 Dose of Dose of Compound No. 23 Kresoxim-Methyl 12.5 g/ha 6.3g/ha 3.1 g/ha 0 g/ha 100 g/ha  0(4)    5.0 15.0(5)  5.0 50 g/ha 2.5(12) 7.5(15)  7.5(15) 15.0 25 g/ha  0(24) 10.0(30)  20.0(30) 30.0  0 g/ha80.0 100 100

TABLE 6 Dose of Dose of Compound No. 35 Kresoxim-Methyl 6.3 g/ha 3.1g/ha 1.6 g/ha 0 g/ha 100 g/ha 0(1) 0(1.5) 0(4.5) 10  50 g/ha  5  52(6.8) 15  0 g/ha 10 15 45

TABLE 7 Dose of Dose of Compound No. 39 Kresoxim-Methyl 12.5 g/ha 6.3g/ha 3.1 g/ha 0 g/ha 100 g/ha  0(1.7)   0(3.0) 2.5(3.0) 5.0 50 g/ha0(5.2) 2.5(9.0) 2.5(9.0) 15.0 25 g/ha  0(10.5)  5.0(18.0) 30.0 30.0  0g/ha 35.0 60.0 60.0

TABLE 8 Dose of Dose of Compound No. 40 Kresoxim-Methyl 6.3 g/ha 3.1g/ha 1.6 g/ha 0 g/ha 100 g/ha  0(4.5)  0(6.7)  0(6.7) 15.0 50 g/ha0(9.7) 5.0(14.6) 5.0(14.6) 32.5 25 g/ha 0(9.7) 7.5(14.6) 15.0 32.5  0g/ha 30.0 45.0 45.0

TABLE 9 Dose of Dose of Compound No. 23 Spiroxamine 12.5 g/ha 6.3 g/ha3.1 g/ha 0 g/ha 100 g/ha    0(26.0) 7.5(32.5) 35.0 32.5 50 g/ha15.0(36.0)   52.5 80.0(45.0) 45.0 25 g/ha 52.5(80.0) 80.0(100)   80(100) 100  0 g/ha 80.0 100 100

TABLE 10 Dose of Dose of Compound No. 35 Spiroxamine 6.3 g/ha 3.1 g/ha1.6 g/ha 0 g/ha 100 g/ha  0(2) 0(3) 2(9) 20 50 g/ha 0(6) 5(9) 10(27) 6025 g/ha 5(8) 10(12) 30(36) 80  0 g/ha 10 15 45

TABLE 11 Dose of Dose of Compound No. 39 Spiroxamine 12.5 g/ha 6.3 g/ha3.1 g/ha 0 g/ha 100 g/ha  0(11.3)   0(19.5)   0(19.5) 32.5  50 g/ha 0(15.7) 15.0(27.0) 15.0(27.0) 45.0  25 g/ha 2.5(35)   15.0(60.0)20.0(60.0) 100  0 g/ha 35.0 60.0 60.0

TABLE 12 Dose of Dose of Compound No. 40 Spiroxamine 6.3 g/ha 3.1 g/ha1.6 g/ha 0 g/ha 100 g/ha 0(5.2)    0(7.8) 2.5(7.8) 17.5  50 g/ha 0(24.0)17.5(36.0) 20.0(36.0) 80.0  25 g/ha 0(30.0)  7.5(45.0) 35.0(45.0) 100  0g/ha 30.0 45.0 45.0

TABLE 13 Dose of Dose of Compound No. 23 Epoxiconazole 12.5 g/ha 6.3g/ha 3.1 g/ha 0 g/ha 3.1 g/ha 35(36) 20(60)  45(60)  60 1.6 g/ha 55(60)35(100) 60(100) 100   0 g/ha 60 100 100

TABLE 14 Dose of Dose of Compound No. 35 Epoxiconazole 6.3 g/ha 3.1 g/ha1.6 g/ha 0 g/ha 6.3 g/ha  0(4.5)   0(6.8)   10(20.3) 45 3.1 g/ha 0(10)15 30(45) 100 1.6 g/ha 2(10) 10(15) 20(45) 100   0 g/ha 10 15 45

TABLE 15 Dose of Dose of Compound No. 39 Epoxiconazole 12.5 g/ha 6.3g/ha 3.1 g/ha 0 g/ha 6.3 g/ha  0(1.5)   0(3.2) 15.0 5.0 3.1 g/ha2.5(18.0) 15.0(39.0) 20.0(48.0) 60.0 1.6 g/ha 7.5(30.0) 20.0(65.0)65.0(80.0) 100   0 g/ha 30.0 65.0 80.0

TABLE 16 Dose of Dose of Compound No. 40 Epoxiconazole 6.3 g/ha 3.1 g/ha1.6 g/ha 0 g/ha 6.3 g/ha 2.5(30.0) 2.5(45.0) 30.0(45.0) 100 3.1 g/ha7.5(30.0) 60.0 45.0 100   0 g/ha 30.0 45.0 45.0

TABLE 17 Dose of Dose of Compound No. 23 Tebuconazole 12.5 g/ha 6.3 g/ha3.1 g/ha 0 g/ha 12.5 g/ha 15.0(48.0)  30.0(80.0)  55.0(80.0) 80.0  6.3g/ha 55.0(60.0) 35.0(100) 52.5(100) 100  3.1 g/ha 45.0(60.0) 65.0(100)80.0(100) 100   0 g/ha 60.0 100 100

TABLE 18 Dose of Dose of Compound No. 35 Tebuconazole 6.3 g/ha 1.6 g/ha0 g/ha 12.5 g/ha   0(4.5)   20(20.3) 45  6.3 g/ha 0(6) 30 60  3.1 g/ha5(8) 30(36) 80   0 g/ha 10 45

TABLE 19 Dose of Dose of Compound No. 39 Tebuconazole 12.5 g/ha 6.3 g/ha3.1 g/ha 0 g/ha 12.5 g/ha 5.0(24.0) 5.0(52.0) 45.0(64.0) 80.0  6.3 g/ha5.0(30.0) 7.5(65.0)  7.5(80.0) 100  3.1 g/ha 5.0(30.0) 10.0(65.0) 20.0(80.0) 100   0 g/ha 30.0 65.0 80.0

TABLE 20 Dose of Dose of Compound No. 40 Tebuconazole 6.3 g/ha 3.1 g/ha0 g/ha 12.5 g/ha 15(24) 30(36) 80  6.3 g/ha 20(24) 30(36) 80   0 g/ha 3045

TABLE 21 Dose of Dose of Compound No. 23 Quinoxyfen 12.5 g/ha 6.3 g/ha3.1 g/ha 0 g/ha 6.3 g/ha 2.5(10.5) 15.0(17.5) 17.5 17.5 1.6 g/ha5.0(48.0) 65.0(80.0) 55.0(80.0) 80.0   0 g/ha 60.0 100 100  

TABLE 22 Dose of Dose of Compound No. 35 Quinoxyfen 6.3 g/ha 3.1 g/ha1.6 g/ha 0 g/ha 6.3 g/ha   0(0.5)   0(1.1) 0(1.4) 2.4 3.1 g/ha  2.42.4(3.2) 0(4.3) 7.3 1.6 g/ha 2.4(8.6)   0(19.4)  0(25.9) 44.1   0 g/ha19.6 44.1 58.8

TABLE 23 Dose of Dose of Compound No. 39 Quinoxyfen 12.5 g/ha 6.3 g/ha3.1 g/ha 0 g/ha 6.3 g/ha    0(5.2) 2.5(11.3) 2.5(14)  17.5 3.1 g/ha2.5(6)  7.5(13.0) 20.0 20.0 1.6 g/ha 5.0(24) 5.0(52.0) 35.0(64.0) 80.0  0 g/ha 30.0 65.0 80.0

TABLE 24 Dose of Dose of Compound No. 40 Quinoxyfen 6.3 g/ha 3.1 g/ha1.6 g/ha 0 g/ha 6.3 g/ha 0(9.0) 2.5(13.5)  5.0(13.5) 30.0 3.1 g/ha0(9.0) 5.0(13.5) 10.0(13.5) 30.0 1.6 g/ha 2.5(18.0)  20.0(27.0) 20.0(27.0) 60.0   0 g/ha 30.0 45.0 45.0

TABLE 25 Dose of Dose of Compound No. 35 Metrafenone 6.3 g/ha 3.1 g/ha1.6 g/ha 0 g/ha 12.5 g/ha  17.5(36.0) 20.0(60.0) 45.0(60.0) 60.0 6.3g/ha 20.0(48.0) 35.0(80.0) 45.0(80.0) 80.0 3.1 g/ha 32.5(60.0)35.0(100)  80.0(100)  100   0 g/ha 60.0 100 100

TABLE 26 Dose of Dose of Compound No. 23 Propiconazole 6.3 g/ha 3.1 g/ha0 g/ha 6.3 g/ha 0(1) 0(6) 20 3.1 g/ha 0(5) 10(30) 100   0 g/ha 5 30

TABLE 27 Dose of Dose of Compound No. 35 Propiconazole 6.3 g/ha 3.1 g/ha1.6 g/ha 0 g/ha 12.5 g/ha  0(0.8)   0(2.2)   0(7.0) 11.6 6.3 g/ha 6.7 4.2(11.5)  9.1(36.8) 60.7 3.1 g/ha 9.0 11.6(19.0) 46.0(60.7) 100   0g/ha 6.7 19.0 60.7

TABLE 28 Dose of Dose of Compound No. 39 Propiconazole 6.3 g/ha 3.1 g/ha0 g/ha 6.3 g/ha 0(3.5)  0(3.5) 20.0 3.1 g/ha  0(17.5) 2.5(17.5) 100   0g/ha 17.5 17.5

TABLE 29 Dose of Dose of Compound No. 40 Propiconazole 3.1 g/ha 1.6 g/ha0 g/ha 6.3 g/ha 0(4)  0(1) 20 3.1 g/ha 0(20) 7.5 100   0 g/ha 20 5  

TABLE 30 Dose of Dose of Compound No. 23 Triadimenol 6.3 g/ha 3.1 g/ha 0g/ha 6.3 g/ha   0(27.0)   0(45.0) 45.0 3.1 g/ha 5.0(39.0) 7.5(65.0) 65.0  0 g/ha 60.0 100

TABLE 31 Dose of Dose of Compound No. 35 Triadimenol 6.3 g/ha 3.1 g/ha1.6 g/ha 0 g/ha 12.5 g/ha 0(1.3)  0(3.6)   0(11.5) 19.0  6.3 g/ha 6.74.2(10.6) 6.7(33.9) 55.8   0 g/ha 6.7 19 60.7

TABLE 32 Dose of Dose of Compound No. 39 Triadimenol 6.3 g/ha 3.1 g/ha 0g/ha 6.3 g/ha 5(13.5)  2.5(29.3) 45.0 3.1 g/ha 30.0 17.5(42.3) 65.0   0g/ha 30.0 65.0

TABLE 33 Dose of Dose of Compound No. 40 Triadimenol 3.1 g/ha 1.6 g/ha 0g/ha 6.3 g/ha 0(9)  5(20.3) 45 3.1 g/ha  0(13) 15(29.3) 65   0 g/ha 2045

TABLE 34 Dose of Dose of Compound No. 23 Cyproconazole 6.3 g/ha 3.1 g/ha0 g/ha 6.3 g/ha   0(0.75)   0(4.5) 15 3.1 g/ha 0(4) 10(24) 80   0 g/ha 530

TABLE 35 Dose of Dose of Compound No. 35 Cyproconazole 6.3 g/ha 3.1 g/ha1.6 g/ha 0 g/ha 12.5 g/ha    0(0.38)   0(1.5)   0(12.0) 15.0 6.3 g/ha  0(1.6) 5.0(6.5) 7.5(5.2) 65.0 3.1 g/ha 2.5(2.5) 10.0(10.0) 20.0(80.0)100   0 g/ha 2.5 10.0 80.0

TABLE 36 Dose of Dose of Compound No. 39 Cyproconazole 6.3 g/ha 3.1 g/ha0 g/ha 6.3 g/ha 0(2.6)    0(2.6) 15.0 3.1 g/ha 0(14.0) 10.0(14.0) 80.0  0 g/ha 17.5 17.5

TABLE 37 Dose of Dose of Compound No. 40 Cyproconazole 3.1 g/ha 1.6 g/ha0 g/ha 6.3 g/ha 0(3.0)    0(0.8) 15.0 3.1 g/ha 0(16.0) 2.5(4.0) 80.0   0g/ha 20.0 5.0

TABLE 38 Dose of Dose of Compound No. 23 Fluquinconazole 6.3 g/ha 3.1g/ha 0 g/ha 200 g/ha 5.0(4.5) 5.0(7.5) 7.5 100 g/ha 5.0(6.0)  7.5(10.0)10.0  50 g/ha  5.0(18.0) 10.0(30.0) 30.0  0 g/ha 60.0 100

TABLE 39 Dose of Dose of Compound No. 35 Fluquinconazole 6.3 g/ha 3.1g/ha 1.6 g/ha 0 g/ha 400 g/ha  0(0.06) 2.5   0(2.0) 2.5 200 g/ha 0(0.2)2.5 2.5(6.0) 7.5 100 g/ha 0(0.5) 0(2.0)  2.5(16.0) 20.0  0 g/ha 2.510.0  80.0

TABLE 40 Dose of Dose of Compound No. 39 Fluquinconazole 6.3 g/ha 3.1g/ha 0 g/ha 200 g/ha   0(2.2)  7.5 7.5 100 g/ha 2.5(3)   5.0(6.5) 10.0 50 g/ha 5.0(9.0)  2.5(19.5) 30.0  0 g/ha 30.0 65.0

TABLE 41 Dose of Dose of Compound No. 40 Fluquinconazole 3.1 g/ha 1.6g/ha 0 g/ha 50 g/ha 0 (6.0) 10.0 (13.5) 30.0  0 g/ha 20.0 45.0

TABLE 42 Dose of Dose of Compound No. 23 Fenpropidin 6.3 g/ha 3.1 g/ha 0g/ha 50 g/ha 5.0 (36.0)  7.5 (60.0) 60.0 25 g/ha 5.0 (48.0) 80.0 80.012.5 g/ha   65.0 35.0 (100) 100  0 g/ha 60.0 100

TABLE 43 Dose of Dose of Compound No. 35 Fenpropidin 3.1 g/ha 1.6 g/ha 0g/ha 50 g/ha 2.5 (3.0) 2.5 (9.0)  30.0 25 g/ha 2.5 (6.0) 7.5 (18.0) 60.012.5 g/ha   2.5 (6.0) 7.5 (18.0) 60.0  0 g/ha 10.0 30.0

TABLE 44 Dose of Dose of Compound No. 39 Fenpropidin 6.3 g/ha 3.1 g/ha 0g/ha 50 g/ha  7.5 (18.0)  5.0 (39.0) 60.0 25 g/ha 20.0 (24.0) 30.0(52.0) 80.0 12.5 g/ha   20.0 (30.0) 45.0 (65.0) 100  0 g/ha 30.0 65.0

TABLE 45 Dose of Dose of Compound No. 40 Fenpropidin 3.1 g/ha 1.6 g/ha 0g/ha 50 g/ha   0 (12.0) 5.0 (27.0) 60.0 25 g/ha 15.0 (16.0) 2.5 (36.0)80.0 12.5 g/ha   17.5 (20.0) 7.5 (45.0) 100  0 g/ha  20.0 45.0

TABLE 46 Dose of Dose of Compound No. 23 Metconazole 12.5 g/ha 6.3 g/ha3.1 g/ha 0 g/ha 6.3 g/ha 0 (0.2) 0 (1.4)  7.3 4.9 3.1 g/ha 0 (0.9) 0(5.8) 4.9 (6.2) 19.6   0 g/ha 4.9 29.4 31.8

TABLE 47 Dose of Dose of Compound No. 35 Metconazole 6.3 g/ha 3.1 g/ha1.6 g/ha 0 g/ha 6.3 g/ha 0 (1.0)   0 (2.2) 2.4 (2.9) 4.9 3.1 g/ha 0(3.8) 4.9 (8.6)  7.5 (11.5) 19.6 1.6 g/ha 14.7 (8.6)   17.1 (19.4) 44.144.1   0 g/ha 19.6 44.1 58.8

TABLE 48 Dose of Dose of Compound No. 39 Metconazole 6.3 g/ha 3.1 g/ha1.6 g/ha 0 g/ha 3.1 g/ha  4.9 4.9 (8.6)  7.3 (11.5) 19.6 1.6 g/ha 2.4(8.6) 4.9 (19.4) 7.3 (25.9) 44.1   0 g/ha 19.6 44.1 58.8

TABLE 49 Dose of Dose of Compound No. 40 Metconazole 6.3 g/ha 3.1 g/ha 0g/ha 6.3 g/ha 0 (0.7)   0 (0.8) 4.9 1.6 g/ha 0 (6.4) 4.9 (7.5) 44.1   0g/ha 14.7 17.1

TABLE 50 Dose of Dose of Compound No. 23 Tetraconazole 6.3 g/ha 3.1 g/ha0 g/ha 6.3 g/ha   0 (1.75) 5.0 (10.5) 35.0 3.1 g/ha 2.5 (4.0) 7.5 (24.0)80.0   0 g/ha 5.0 30.0

TABLE 51 Dose of Dose of Compound No. 35 Tetraconazole 3.1 g/ha 1.6 g/ha0 g/ha 6.3 g/ha 0(10.5)   0(21.0) 35.0 3.1 g/ha 0(24.0) 5.0(48.0) 80.0  0 g/ha 30.0 60.0

TABLE 52 Dose of Dose of Compound No. 39 Tetraconazole 6.3 g/ha 3.1 g/ha0 g/ha 6.3 g/ha  0(6.1) 2.5(6.1) 35.0 3.1 g/ha 2.5(14.0)  7.5(14.0) 80.0  0 g/ha 17.5 17.5

TABLE 53 Dose of Dose of Compound No. 40 Tetraconazole 3.1 g/ha 1.6 g/ha0 g/ha 6.3 g/ha 0(3.5)    0(1.8) 35.0 3.1 g/ha 0(16.0) 15.0(4.0) 80.0  0 g/ha 20.0 5.0

Test Example 2 Test on Preventive Effect Against Cucumber Powdery Mildew

Cucumber (cultivar: Suyo) was cultivated in a plastic pot having adiameter of 7.5 cm, and when it reached 1.5-leaf stage, 10 ml of achemical solution having the compound of the present invention adjustedto a prescribed concentration, was applied by a spray gun. After thechemical solution dried, a suspension of conidia of Sphaerothecacucurbitae was sprayed and inoculated and maintained in a constanttemperature chamber at 20° C. From 6 to 11 days after the inoculation,the area of sporulation was investigated, and the disease rate wasdetermined in the same manner as in Test Example 3, and the results areshown in Tables 54 to 96. The average lesion area in the non-treatedplot was determined in the same manner as for the treated plot exceptthat water was applied by a spray gun instead of the chemical solution.

Further, theoretical values by the Colby's formula are shown in bracketsin Tables 54 to 96. TABLE 54 Triflumizole Compound No. 23 concentrationconcentration 8 ppm 4 ppm 2 ppm 0 ppm 31 ppm   0(2.0) 0(2.1)   0(2.4)2.4 16 ppm 54.3(57.9) 64.2 64.2(69.1) 69.1  0 ppm 83.9 88.9 100

TABLE 55 Triflumizole Compound No. 35 concentration concentration 4 ppm2 ppm 1 ppm 0 ppm 31 ppm   0(14.3) 0(16.1)   0(17.7) 17.7 16 ppm12.6(57.3) 70.8 45.5(70.8) 70.8  0 ppm 80.9 91.0 100

TABLE 56 Triflumizole Compound No. 39 concentration concentration 16 ppm8 ppm 4 ppm 0 ppm 16 ppm  0(6.0)  7.5 7.5(24)  30.0 8 ppm 5(16.0)17.5(24.0) 45.0(64.0) 80.0 0 ppm 20.0 30.0  80.0

TABLE 57 Triflumizole Compound No. 40 concentration concentration 4 ppm2 ppm 1 ppm 0 ppm 16 ppm  35.4(57.9) 49.4(64.8) 34.5(69.1) 69.1 8 ppm49.7(74.5) 74.1(83.3) 83.9(88.9) 88.9 0 ppm 83.9 93.8 100

TABLE 58 Compound No. 23 Mepanipyrim concentration concentration 8 ppm 0ppm 16 ppm  39.5(41.4) 49.4 8 ppm 59.2(83.9) 100 4 ppm 74.1(83.9) 100 0ppm 83.9

TABLE 59 Mepanipyrim Compound No. 35 concentration concentration 4 ppm 2ppm 1 ppm 0 ppm 16 ppm  40.4(61.3) 60.7(69.0) 60.7(75.8) 75.8 8 ppm25.3(80.9) 100   96.1(100)  100 4 ppm 55.6(77.7) 85.9(87.5) 91.0(96.1)96.1 0 ppm 80.9 91.0 100

TABLE 60 Mepanipyrim Compound No. 39 concentration concentration 16 ppm4 ppm 0 ppm 16 ppm  7.5(16.0) 45.0(64.0) 80.0 8 ppm 2.5(20.0) 60.0(80.0)100 4 ppm 17.5(20.0)  60.0(80.0) 100 0 ppm 20.0 80.0

TABLE 61 Compound No. 40 Mepanipyrim concentration concentration 4 ppm 0ppm 16 ppm  14.8(41.4) 49.4 8 ppm 64.2(83.9) 100 0 ppm 83.9

TABLE 62 Iminoctadine Compound No. 23 albesilate concentrationconcentration 2 ppm 0 ppm 8 ppm 79.0(83.9) 83.9 0 ppm 100

TABLE 63 Iminoctadine albesilate Compound No. 35 concentrationconcentration 4 ppm 2 ppm 1 ppm 0 ppm 16 ppm  2.5(28.6) 15.1(32.1)22.8(35.3) 35.3 8 ppm 7.6(49.1) 55.6 25.3(60.7) 60.7 4 ppm 7.6(69.5)70.8(78.2) 91.0(85.9) 85.9 0 ppm 80.9 91.0 100

TABLE 64 Iminoctadine albesilate Compound No. 39 concentrationconcentration 16 ppm 8 ppm 4 ppm 0 ppm 16 ppm  2.5(6.0) 7.5(9.0) 10.0(24.0) 30.0 8 ppm 2.5(9.0) 7.5(13.5) 30.0(36.0) 45.0 0 ppm 20.0 30.080.0

TABLE 65 Iminoctadine albesilate Compound No. 40 concentrationconcentration 4 ppm 2 ppm 1 ppm 0 ppm 16 ppm   7.4(41.4) 19.7(46.3)44.4(49.4) 49.4 4 ppm 74.1(78.6) 83.9(87.9) 88.9(93.8) 93.8 0 ppm 83.993.8 100

TABLE 66 Oxpoconazole fumarate Compound No. 35 concentrationconcentration 4 ppm 2 ppm 1 ppm 0 ppm 31 ppm  5.1(36.8) 20.2(41.4)35.4(45.5) 45.5 16 ppm 45.5(80.9) 75.8(91.0) 100 100  8 ppm 60.7(80.9)85.9(91.0) 80.9(100)  100  0 ppm 80.9 91.0 100

TABLE 67 Oxpoconazole fumarate Compound No. 39 concentrationconcentration 16 ppm 8 ppm 4 ppm 0 ppm 31 ppm  0(6.0) 7.5(9)   7.5(24.0) 30.0 16 ppm   0(12.0) 30.0 45.0(48.0) 60.0  8 ppm 2.5(16.0)17.5(24.0) 60.0(64.0) 80.0  0 ppm 20.0 30.0 80.0

TABLE 68 Compound No. 23 Azoxystrobin concentration concentration 16 ppm0 ppm 63 ppm  8.4(30.7) 100 31 ppm 10.9(30.7) 100  0 ppm 30.7

TABLE 69 Azoxystrobin Compound No. 35 concentration concentration 4 ppm2 ppm 1 ppm 0 ppm 63 ppm 9.3(11.7) 65.7 80.4 100 31 ppm 21.6 31.4(52.8)31.4(64.6) 80.4  0 ppm 11.7 65.7 80.4

TABLE 70 Azoxystrobin Compound No. 39 concentration concentration 16 ppm8 ppm 4 ppm 0 ppm 125 ppm  5.0(20.0) 45.0 80.0 100 63 ppm 7.5(20.0) 45.045.0(80.0) 100 31 ppm 5.0(20.0) 20.0(30.0) 60.0(80.0) 100  0 ppm 20.030.0 80.0

TABLE 71 Compound No. 40 Azoxystrobin concentration concentration 2 ppm1 ppm 0 ppm 63 ppm 60.4(80.2) 100 100  0 ppm 80.2 100

TABLE 72 Polyoxins Compound No. 23 concentration concentration 16 ppm 8ppm 4 ppm 0 ppm 125 ppm  3.4(18.5) 10.9(27.4) 30.7(36.4) 60.4 63 ppm5.9(30.7) 20.8(45.5) 30.7(60.4) 100 31 ppm 5.9(30.7) 20.8(45.5) 60.4 100 0 ppm 30.7 45.5 60.4

TABLE 73 Polyoxins Compound No. 35 concentration concentration 4 ppm 2ppm 1 ppm 0 ppm 125 ppm  0(2.5)  4.4(14.2) 11.7(17.3) 21.6 63 ppm 16.731.4 31.4(37.0) 46.1 31 ppm 16.7 31.4(52.8) 60.8(64.6) 80.4  0 ppm 11.765.7 80.4

TABLE 74 Polyoxins Compound No. 39 concentration concentration 16 ppm 8ppm 4 ppm 0 ppm 125 ppm  2.5(6.0) 10.0 30.0 30.0 63 ppm 2.5(9.0) 20.045.0 45.0 31 ppm 7.5(16.0) 20.0(24.0) 45.0(64.0) 80.0  0 ppm 20.0 30.080.0

TABLE 75 Polyoxins Compound No. 40 concentration concentration 4 ppm 2ppm 1 ppm 0 ppm 125 ppm  10.8(18.5) 45.5(48.4) 45.5(60.4) 60.4 63 ppm30.7 30.7(80.2) 45.5(100) 100 31 ppm 35.6 45.5(80.2) 80.2(100) 100  0ppm 30.7 80.2 100

TABLE 76 Cyazofamid Compound No. 23 concentration concentration 16 ppm 8ppm 4 ppm 0 ppm 125 ppm  18.3(30.7) 45.5 80.2 100 63 ppm  8.4(30.7)30.7(45.5) 45.5(60.4) 100 31 ppm 10.9(30.7) 30.7(45.5) 60.4 100  0 ppm30.7 45.5 60.4

TABLE 77 Cyazofamid Compound No. 35 concentration concentration 4 ppm 2ppm 1 ppm 0 ppm 125 ppm 9.3(9.4) 31.4(52.8) 46.1(64.6) 80.4  63 ppm 11.746.1(65.7) 80.4 100  0 ppm 11.7 65.7 80.4

TABLE 78 Cyazofamid Compound No. 39 concentration concentration 16 ppm 8ppm 4 ppm 0 ppm 125 ppm  0(20) 20(30)  80 100 63 ppm 5(20) 65 100 100 31ppm 0(20) 45 60(80) 100  0 ppm 20 30  80

TABLE 79 Cyazofamid Compound No. 40 concentration concentration 2 ppm 1ppm 0 ppm 125 ppm 100 65.4(100) 100  63 ppm 45.5(80.2) 80.2(100) 100  0ppm 80.2 100

TABLE 80 Chlorothalonil Compound No. 23 concentration concentration 16ppm 4 ppm 0 ppm 125 ppm   8.4(30.7) 65.4 100 63 ppm 18.3(30.7) 80.2 10031 ppm 20.8(30.7) 45.5(60.4) 100  0 ppm 30.7 60.4

TABLE 81 Chlorothalonil Compound No. 35 concentration concentration 2ppm 1 ppm 0 ppm 125 ppm  65.7 46.1(80.4) 100 63 ppm 55.9 55.9(64.6) 80.431 ppm 36.3(52.8) 31.4(64.6) 80.4  0 ppm 65.7 80.4

TABLE 82 Chlorothalonil Compound No. 39 concentration concentration 16ppm 8 ppm 4 ppm 0 ppm 125 ppm  2.5(12.0) 30.0 30.0(48.0) 60.0 63 ppm2.5(16.0) 20.0(24.0) 30.0(64.0) 80.0 31 ppm 5.0(16.0) 20.0(24.0)45.0(64.0) 80.0  0 ppm 20.0 30.0 80.0

TABLE 83 Chlorothalonil Compound No. 40 concentration concentration 4ppm 2 ppm 1 ppm 0 ppm 125 ppm  8.4(30.7) 20.8(80.2) 65.4(100) 100 63 ppm45.5 45.5(80.2) 100 100 31 ppm 30.7 60.4(80.2) 60.4 100  0 ppm 30.7 80.2100

TABLE 84 Compound No. 23 Imibenconazole concentration concentration 16ppm 0 ppm 8 ppm 20.8(30.7) 100 4 ppm 20.8(30.7) 100 0 ppm 30.7

TABLE 85 Compound No. 35 Imibenconazole concentration concentration 16ppm 0 ppm 16 ppm  31.4(52.8) 65.7 4 ppm 31.4(64.6) 80.4 0 ppm 80.4

TABLE 86 Imibenconazole Compound No. 39 concentration concentration 16ppm 4 ppm 0 ppm 16 ppm  5.0(12.0) 30.0 60.0 8 ppm 2.5(20.0) 45.0(80.0)100 4 ppm 2.5(20.0) 65.0(80.0) 100 0 ppm 20.0 80.0

TABLE 87 Imibenconazole Compound No. 40 concentration concentration 2ppm 1 ppm 0 ppm 16 ppm  35.6(64.3) 60.4(80.2) 80.2 8 ppm 60.4(80.2)80.2(100)  100 0 ppm 80.2 100

TABLE 88 Tebuconazole Compound No. 23 concentration concentration 8 ppm4 ppm 0 ppm 4 ppm 1.8(5.0) 12.4(40.3) 71.0 2 ppm 3.6(4.0)  1.8(32.3)56.8 0 ppm 7.1 56.8

TABLE 89 Tebuconazole Compound No. 35 concentration concentration 2 ppm1 ppm 0 ppm 4 ppm 24.6 39.1(40.3) 71.0 2 ppm  7.1(8.1) 32.0(32.3) 56.8 0ppm 14.2 56.8

TABLE 90 Tebuconazole Compound No. 39 concentration concentration 8 ppm4 ppm 0 ppm 4 ppm 1.8(10.1)  3.6(22.7) 71.0 2 ppm 3.6(8.1)  24.9(18.2)56.8 0 ppm 14.2 32.0

TABLE 91 Tebuconazole Compound No. 40 concentration concentration 2 ppm1 ppm 0 ppm 4 ppm 7.1(30.2) 37.3(50.4) 71.0 0 ppm 42.6 71.0

TABLE 92 Compound No. 23 Tetraconazole concentration concentration 4 ppm0 ppm 4 ppm 21.3(32.3) 56.8 2 ppm 14.2(32.3) 56.8 0 ppm 56.8

TABLE 93 Compound No. 35 Tetraconazole concentration concentration 2 ppm1 ppm 0 ppm 4 ppm 14.2 14.2(32.3) 56.8 2 ppm 7.1(8.1) 32.0(32.3) 56.8 0ppm 14.2 56.8

TABLE 94 Compound No. 39 Tetraconazole concentration concentration 8 ppm4 ppm 0 ppm 4 ppm 1.8(8.1) 39.1 56.8 2 ppm 1.8(8.1) 5.3(18.2) 56.8 0 ppm14.2 32.0

TABLE 95 Tetraconazole Compound No. 40 concentration concentration 2 ppm1 ppm 0 ppm 4 ppm 14.2(24.2)  5.3(40.3) 56.8 2 ppm 21.3(24.2) 12.4(40.3)56.8 0 ppm 42.6 71.0

TABLE 96 Oxpoconazole Compound No. 23 concentration concentration 16 ppm8 ppm 4 ppm 0 ppm 8 ppm 0(1.1) 4.9(8.8) 19.8(35.2) 44.5 0 ppm 2.4 19.879.2

Now, Formulation Examples of the present invention will be describedbelow. However, the blend ratio, type of formulation or the like of thepresent invention is by no means restricted to the following Examples.

Formulation Example 1

(a) Kaolin 78 parts by weight (b) Condensate of β-naphthalenesulfonicacid  2 parts by weight sodium salt with formalin (c) Polyoxyethylenealkylaryl sulfate  5 parts by weight (d) Hydrated amorphous silicondioxide 15 parts by weight

A mixture of the above components, the compound of the formula (I) andEpoxiconazole are mixed in a weight ratio of 8:1:1 to obtain a wettablepowder.

Formulation Example 2

(a) Compound of the formula (I) 0.5 part by weight (b) Epoxiconazole 0.5part by weight (c) Bentonite 20 parts by weight (d) Kaolin 74 parts byweight (e) Sodium lignin sulfonate 5 parts by weight

An appropriate amount of water for granulation is added to the abovecomponents and mixed, and the mixture is granulated to obtain granules.

Formulation Example 3

(a) Compound of the present invention 2 parts by weight (b)Epoxiconazole 3 parts by weight (c) Talc 95 parts by weight 

The above components are uniformly mixed to obtain a dust.

The entire disclosures of Japanese Patent Application No. 2003-371863filed on Oct. 31, 2003, Japanese Patent Application No. 2004-006355filed on Jan. 14, 2004 and Japanese Patent Application No. 2004-210174filed on Jul. 16, 2004 including specifications, claims and summariesare incorporated herein by reference in their entireties.

1. A fungicidal composition containing as active ingredients (a) abenzoylpyridine derivative represented by the formula (I) or its salt:

(wherein X is a halogen atom, a nitro group, a substitutable alkoxygroup, a substitutable aryloxy group, a substitutable cycloalkoxy group,a hydroxyl group, a substitutable hydrocarbon group, a substitutablealkylthio group, a cyano group, a carboxyl group which may be esterifiedor amidated, or a substitutable amino group, n is 1, 2, 3 or 4; R¹ is asubstitutable alkyl group, R^(2′) is a substitutable alkyl group, asubstitutable alkoxy group, a substitutable aryloxy group, asubstitutable cycloalkoxy group or a hydroxyl group, p is 1, 2 or 3, andR^(2′) is a substitutable alkoxy group or a hydroxyl group, providedthat at least two of R^(2′) and R^(2″) may form a condensed ringcontaining an oxygen atom) and (b) at least one fungicide selected fromthe group consisting of a strobilurin compound, an azole compound, amorpholine compound, a pyrimidinamine compound, a guanidine compound, anorganic chlorine compound, an imidazole compound, an antibiotic, apyridinamine compound, a quinoxaline compound, a dithiocarbamatecompound, a cyanoacetamide compound, a phenylamide compound, a sulfenicacid compound, a copper compound, an isoxazole compound, anorganophosphorus compound, a N-halogenothioalkyl compound, adicarboxyimide compound, a benzanilide compound, piperazine compound, apyridine compound, a carbinol compound, a piperidine compound, anorganotin compound, an urea compound, a cynnamic acid compound, a phenylcarbamate compound, a cyanopyrrole compound, an oxazolidinone compound,a thiazole carboxyamide compound, a silyl amide compound, an aminoacidamidecarbamate compound, an imidazolidine compound, a hydroxyanilidecompound, an oxime ether compound, a phenoxyamide compound, abenzophenone compound, Isoprothiolane, Pyroquilon, Dichlomezine,Quinoxyfen, Propamocarb Hydrochloride, Chloropicrin, Dazomet,Metam-sodium, Nicobifen, Diclocymet and Proquinazid.
 2. The fungicidalcomposition according to claim 1, wherein the fungicide (b) is at leastone member selected from the group consisting of Kresoxim-Methyl,Azoxystrobin, Metominofen, Trifloxystrobin, Picoxystrobin, Oryzastrobin,Dimoxystrobin, Fluoxastrobin, Epoxiconazole, Triflumizole, Oxpoconazolefumarate, Tebuconazole, Imibenconazole, Tetraconazole, Triadimefon,Bitertanol, Etaconazole, Propiconazole, Penconazole, Flusilazole,Myclobutanil, Cyproconazole, Hexaconazole, Furconazole cis, Prochloraz,Metconazole, Sipconazole, Prothioconazole, Simeconazole, Tricyclazole,Probenazole, Fluquinconazole, Triadimenol, Fenpropimorph, Spiroxamine,Mepanipyrim, Pyrimethanil, Cyprodinil, Iminoctadine, Chlorothalonil,Fthalide, Quintozene, Cyazofamid, Benomyl, Thiophanate-Methyl,Carbendazim, Polyoxins, Fluazinam, Quinomethionate, Maneb, Zineb,Mancozeb, Polycarbamate, Metiram, Propineb, Cymoxanil, Metalaxyl,Metalaxyl M, oxadixyl, Ofurace, Benalaxyl, Furalaxyl, Cyprofuram,Dichlofluanid, Cupric hydroxide, Oxine Copper, Hymexazol, Fosetyl-Al,Tolcofos-Methyl, S-benzyl O,O-diisopropylphosphorothioate, O-ethylS,S-diphenylphosphorodithioate, aluminum ethyl hydrogen phosphonate,Captan, Captafol, Folpet, Procymidone, Iprodione, Vinclozolin,Flutolanil, Mepronil, Zoxamid, Tiadinil, Triforine, Pyrifenox,Fenarimol, Flutriafol, Fenpropidine, Fentin Hydroxide, Fentin Acetate,Pencycuron, Dimethomorph, Flumorph, Diethofencarb, Fludioxonil,Fenpiclonil, Famoxadone, Ethaboxam, Silthiopham, Iprovalicarb,Benthiavalicarb, Fenamidone, Fenhexamid, Flusulfamid, Cyflufenamid,Fenoxanil, Isoprothiolane, Pyroquilon, Diclomezine, Quinoxyfen,Propamocarb Hydrochloride, Spiroxamine, Chloropicrin, Dazomet,Metam-sodium, Nicobifen, Metrafenone, Diclocymet and Proquinazid.
 3. Thefungicidal composition according to claim 1, wherein fungicide (b) is atleast one member selected from the group consisting of a strobilurincompound, an azole compound, a morpholine compound, a pyrimidinaminecompound, a guanidine compound, an organic chlorine compound, animidazole compound, an antibiotic, a piperidine compound and abenzophenone compound.
 4. The fungicidal composition according to claim3, wherein the fungicide (b) is at least one member selected from thegroup consisting of Kresoxim-Methyl, Azoxystrobin, Epoxiconazole,Triflumizole, Oxpoconazole fumarate, Tebuconazole, Imibenconazole,Tetraconazole, Cyproconazole, Metconazole, Fluquinconazole, Triadimenol,Fenpropimorph, Spiroxamine, Mepanipyrim, Iminoctadine, Chlorothalonil,Cyazofamid, Polyoxins, Fenpropidine and Metrafenone.
 5. The fungicidalcomposition according to claim 1, wherein the benzoylpyridine derivativeis a compound represented by the formula (I′):

(wherein when A is —N═, B is —CX⁴═; when A is —CH═, B is —CN═; each ofX¹ and X² which are independent of each other, is a halogen atom, analkoxy group, a hydroxyl group, an alkyl group, a CF₃ group or analkylthio group; X³ is a hydrogen atom, a halogen atom, an alkoxy group,an alkyl group, a CF₃ group or an alkylthio group; X⁴ is a hydrogenatom, a halogen atom, an alkoxy group, an alkyl group, a CF₃ group or analkylthio group; R¹ is an alkyl group; R^(2′) is an alkoxy group; p is1, 2 or 3; and each of R^(2″) and R^(2′″) is an alkoxy group).
 6. Thefungicidal composition according to claim 5, wherein the benzoylpyridinederivative is a compound represented by the formula (I′-1):

(wherein each of X¹ and X² which are independent of each other, is ahalogen atom, an alkoxy group, a hydroxyl group, an alkyl group, a CF₃group or an alkylthio group; X³ is a hydrogen atom, a halogen atom, analkoxy group, an alkyl group, a CF₃ group or an alkylthio group; R¹ isan alkyl group; R^(2′) is an alkoxy group; p is 1, 2 or 3; and each ofR^(2″) and R^(2′″) is an alkoxy group).
 7. The fungicidal compositionaccording to claim 6, wherein the benzoylpyridine derivative is at leastone member selected from the group consisting of3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-bromo-5-chloro-2-methoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-4-ethyl-2-methoxypyridine,3-(4,5-dimethoxy-2-methylbenzoyl)-4,5-dichloro-2-methoxypyridine,3-(5-ethoxy-4-methoxy-2-methylbenzoyl)-4,5-dichloro-2-methoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-bromo-5-chloro-2-ethoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-ethoxy-4-methylpyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-bromo-4-chloro-2-ethoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-chloro-5-iodo-2-methoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-iodo-2,4-dimethoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylthiopyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2,4-dimethoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-4,5-dibromo-2-methoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-bromo-2-methoxy-5-methylpyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-bromo-4-trifluoromethyl-2-methoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-4,5-dichloro-2-methoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-2,4-dichloro-5-methylpyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-2,4-dichloro-5-iodopyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-fluoro-4-iodo-5-methylpyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-fluoro-4,5-dimethylpyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-methoxy-4,5-dimethylpyridine,3-(2-ethoxy-3,4-dimethoxy-6-methylbenzoyl)-2-ethoxy-4,5-dimethylpyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-4,5-dimethyl-2-methylthiopyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-bromo-4-chloro-2-methoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-chloro-2-methoxy-5-methylpyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-chloro-5-trifluoromethyl-4-methylpyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-trifluoromethyl-2-methoxy-4-methylpyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-2,4-dichloro-5-trifluoromethylpyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-chloro-5-trifluoromethyl-2-methoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-4-ethinyl-2-methoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-4-fluoromethyl-2-methoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-bromo-4-fluoromethyl-2-methoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-fluoromethyl-2-methoxy-5-methylpyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-4-difluoromethyl-2-methoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-ethyl-4-trifluoromethyl-2-methoxypyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-bromo-2-methoxy-4-methylpyridine,3-(2,3,4-trimethoxy-6-methylbenzoyl)-4-trifluoromethyl-2-methoxy-5-methylpyridineand3-(4,5-dimethoxy-2-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine.8. The fungicidal composition according to claim 5, wherein thebenzoylpyridine derivative is a compound represented by the formula(I′-2):

(wherein each of X¹ and X² which are independent of each other, is ahalogen atom, an alkoxy group, a hydroxyl group, an alkyl group, a CF₃group or an alkylthio group; X³ is a hydrogen atom, a halogen atom, analkoxy group, an alkyl group, a CF₃ group or an alkylthio group; X⁴ is ahydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a CF₃group or an alkylthio group; R¹ is an alkyl group; R^(2′) is an alkoxygroup; p is 1, 2 or 3; and each of R^(2″) and R^(2′″) is an alkoxygroup).
 9. The fungicidal composition according to claim 8, wherein thebenzoylpyridine derivative is at least one compound selected from thegroup consisting of4-(2,3,4-trimethoxy-6-methylbenzoyl)-2,5-dichloro-3-trifluoromethylpyridine,4-(2,3,4-trimethoxy-6-methylbenzoyl)-2-chloro-3-trifluoromethyl-5-methoxypyridine,4-(2,3,4-trimethoxy-6-methylbenzoyl)-2-bromo-3-trifluoromethyl-5-methoxypyridine,4-(2,3,4-trimethoxy-6-methylbenzoyl)-2,3,5-trichloropyridine,4-(2,3,4-trimethoxy-6-methylbenzoyl)-3,5-dichloropyridine,4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-chloro-5-methoxypyridine,4-(2,3,4-trimethoxy-6-methylbenzoyl)-2-bromo-3-chloro-5-methoxypyridineand 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-bromo-5-methylpyridine). 10.The fungicidal composition according to claim 1, wherein the mixingweight ratio of the benzoylpyridine derivative or its salt (a) to thefungicide (b) is from 1:10,000 to 10,000:1.
 11. A method for controllingplant diseases, which comprises applying the fungicidal composition asdefined in claim 1 to plants.